This is the first of a set of three papers in the Journal that were to transform the study of drug antagonism (see also Schild, 1949, and Arunlakshana & Schild, 1959). At the time it was written, there was a pressing need for methods that would allow the effectiveness of drugs to be measured and expressed in a consistent and reproducible fashion. As Schild noted in his introduction, the requirement was particularly great for antagonists because of the multiplicity of methods then used and the lack of information about their reproducibility. In this important paper he proposed and validated a new measure of antagonist action, pA. The key principle is that the same sub-maximal response to an agonist is measured first in the absence of antagonist and then in its presence, using a greater concentration of agonist. This was an important departure from early attempts to quantitate drug antagonism by determining the reduction that the antagonist caused in the response to a standard application of agonist. The results of such measurements had proved rather irreproducible, not only from laboratory to laboratory but even between different preparations of the same tissue. Schild was always meticulous in his acknowledgement of the contributions of others, and he makes it clear that his new scale for the expression of drug antagonism was based on the work of Clark & Raventos (1937) who had already recognised the advantages of assessing the effectiveness of antagonists in terms of the multiple by which the agonist concentration had to be increased to overcome the effect of a certain concentration of antagonist. This factor was described as the dose ratio by Gaddum et al., (1955). Schild extended the concept by suggesting that a useful index of the effectiveness of an antagonist would be the value of pAx, the negative logarithm of the concentration of the antagonist that reduces the effect of a multiple dose (x) of an agonist to that of a single dose. Here x is the dose ratio. Though this was to prove an important advance, the paper became a landmark at least as much because of its detailed description of how best to measure the action of antagonists and also because of its searching discussion of the pharmacological applications of such methods. Three points merit particular mention. Schild showed that pA values provided a means of quantifying not only the overall effectiveness of an antagonist but also some of the characteristics of its action, namely, its time dependence and its variation with concentration. It has to be appreciated that Schild defined pA as an experimental measure of antagonist action, independent of theory. Hence pA increases with time following the application of an antagonist. Also, pAx values may or may not vary with the magnitude of the response measured depending on the antagonist's mechanism of action. Moreover, pA values can be calculated whether or not the antagonism is competitive (though their interpretation is much less certain for noncompetitive antagonism, as Arunlakshana & Schild were to discuss in 1959). It follows that the term pA2 should not be regarded simply as another way of expressing the negative logarithm of the dissociation equilibrium constant for the combination of an antagonist with its binding site: this relationship holds only for reversible competitive antagonism, at equilibrium, as shown by Arunlakshana & Schild (1959). The paper described in the greatest detail how the action of antagonists could be evaluated using the isolated guinea-pig ileum preparation, and the procedures that Schild introduced were to be widely adopted. His ‘automatic assay apparatus’ allowed tissues to be exposed to agonist at regular and precisely timed intervals that would not be affected by the whims or distractions of the experimenter. Schild gave great attention to the details of the equipment and made every effort to ensure that his kymograph tracings would reflect accurately the responses of the tissue. Perhaps most importantly, Schild showed how pAx measurements could provide a reproducible and statistically satisfactory index not only of the activity of antagonists but also of their relative selectivity in blocking the responses to agonists of different classes. His famous ‘ladder’ illustration of Fig. 7 allowed both potency and selectivity to be assessed at a glance. As noted, the pA scale was defined in terms of experimental observations, independent of theory. But tucked away in the second of the two small-print sections on p. 197 is a most important prediction: that for simple competitive antagonism, a nine-fold increase of antagonist should be surmountable by a five-fold rise in agonist, between pA2 and pA10. Hence the difference between pA2 and pA10 should be 0.95. Here again Schild is meticulous in his attribution and choice of words. He writes that this result ‘can be shown’ from the mass action equation developed by Gaddum (1937) for a first order reaction. Clearly, his starting point was the Gaddum equation in its simplest form, based on one-for-one competition between agonist and antagonist for a uniform population of binding sites. It is evident that Schild had already appreciated that the assumption of straightforward competition of this kind implied a simple quantitative relationship between the dose ratio and the concentration of antagonist. Further, by then he knew what this relationship was. He was to publish it two years later (Schild, 1949) in the form. Here x is the dose ratio, K2 is an affinity constant, and Bx is the concentration of antagonist that gives rise to a dose ratio of x. This was to become widely known as the Schild equation and it is considered further in the commentary on the third of Schild's papers on the quantitative study of drug antagonism (Arunlakshana & Schild, 1959).
An isolated ductus deferens preparation together with the sympathetic hypogastric nerve of the guinea‐pig is described. While the preparation showed no spontaneous contractions, nerve stimulation produced longitudinal contractions. The responses to successive periods of nerve stimulation remained constant for several hours. After noradrenaline had been added to the bath fluid for 30 min and then the fluid repeatedly changed to wash out the noradrenaline, the effect of nerve stimulation was greatly increased but declined in the course of 1 hr to the original height. Cocaine also increased the response to stimulation. Preparations made from guinea‐pigs which had previously received reserpine responded to nerve stimulation with progressively diminishing contractions. In these circumstances, the administration of noradrenaline restored the response to nerve stimulation to that seen originally.
Human stomach mucosa contains a pharmacologically active acidic lipid which is indistinguishable from (PGE2) prostaglandin E2 by chromatography in 2 different systems, and by other tests. The concentrations present in mucosa are of the order of 1 mcg/g of wet tissue. Concentrations are similar in mucosa of the body and the pyloric part of the stomach; much smaller amounts are present in submucosa and muscle. PGE2 acts directly on both the longitudinal and the circular muscle layers of the human isolated stomach. The longitudinal muscle of the body of the stomach is contracted by doses of PGE2 which may be as low as 2x10 -9 g/ml. In contrast, PGE2 inhibits the contractions of circular muscle caused by acetylcholine or potassium.
An easy and relatively rapid procedure for distinguishihg the ketonic prostaglandins E (PGEs) from the nonketonic prostaglandins F (PGFs) and other hydroxy-acid lipid spasmogens is presented. The method depends on the ability of certain hydrazine derivatives to combine specifically with keto groups. Girard's reagent T (trimethyl-ammonium-acetohydrazide chloride) was used for differentiation. PGFs were unaffected by the reagent, whereas the reagent affected E series prostaglandins by apparently inactivating them. In addition, apparent inactivation also occurred when the reagent was applied to a mixture of the PGEs and PGFs. After treatment of PGEs in aqueous solution with the reagent for 1 hour, at room temperature or 0 degrees centigrade, their extraction into ether on partition at pH 3-4 was reduced. Freezing to -15 degrees centigrade after the 1 hour treatment, and thawing before the ether partition, further reduced the recovery of PGEs. After reagent treatment in these different conditions, PGFs were recovered fully. The presence of a PGE-like ketonic component in the hydroxy-acid constituents of rabbit and cat irins was demonstrated, along with a lower proportion of the ketonic components in ether-purified rabbit cerebral hemisphere extract.
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 3 p. 663-670 Free Access THE EFFECTS OF A NEW BETA-ADRENOCEPTIVE RECEPTOR BLOCKING DRUG ON HEART RATE IN MAN R. C. HILL, R. C. HILL Department of Clinical Pharmacology, Medical Professorial Unit, St. Bartholomew's Hospital, London, E.C.1Search for more papers by this authorP. TURNER, P. TURNER Department of Clinical Pharmacology, Medical Professorial Unit, St. Bartholomew's Hospital, London, E.C.1Search for more papers by this author R. C. HILL, R. C. HILL Department of Clinical Pharmacology, Medical Professorial Unit, St. Bartholomew's Hospital, London, E.C.1Search for more papers by this authorP. TURNER, P. TURNER Department of Clinical Pharmacology, Medical Professorial Unit, St. Bartholomew's Hospital, London, E.C.1Search for more papers by this author First published: March 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00465.xCitations: 11AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References Ahlquist, R. P. (1948). A study of adrenotropic receptors. Am. J. Physiol., 153, 586– 600. Chamberlain, D. A. (1967). The role of sympathetic innervation of the heart in man. M.D. Thesis University of Cambridge. Chamberlain, D. A., Turner, P. & Sneddon, J. M. (1967). Effects of atropine on heart-rate in healthy man. Lancet, 2, 12– 15. Dale, H. H. (1906). On some physiological actions of ergot. J. Physiol. Lond., 34, 163– 206. Haefely, W., Hürlimann, A. & Thoenen, H. (1967). (6,7-dimethyl-α-[(isopropylamino)methyl]-2-benzofuranulmethanol hydrochloride). Some pharmacological actions of the β-adrenolytic agent Ro3 3528. Angiologica, 4, 203– 215. Citing Literature Volume32, Issue3March 1968Pages 663-670 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 1 p. 164-167 Free Access A PNEUMOGRAPH WHICH REGISTERS BOTH VOLUME AND RATE E. C. SAVINI, E. C. SAVINI Department of Pharmacology, Ecole Nationale de Médecine et de Pharmacie, 14-Caen, FranceSearch for more papers by this author E. C. SAVINI, E. C. SAVINI Department of Pharmacology, Ecole Nationale de Médecine et de Pharmacie, 14-Caen, FranceSearch for more papers by this author First published: January 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00440.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume32, Issue1January 1968Pages 164-167 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 3 p. 567-574 Free Access STUDIES ON THE HISTIDINE-HISTAMINE RELATIONSHIP IN VIVO MARGARET A. REILLY, MARGARET A. REILLY Research Center, Rockland State Hospital Orangeburg, New York, U.S.A.Search for more papers by this authorR. W. SCHAYER, R. W. SCHAYER Supported by U.S. Public Health Service grant AM-10155.Search for more papers by this author MARGARET A. REILLY, MARGARET A. REILLY Research Center, Rockland State Hospital Orangeburg, New York, U.S.A.Search for more papers by this authorR. W. SCHAYER, R. W. SCHAYER Supported by U.S. Public Health Service grant AM-10155.Search for more papers by this author First published: March 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00456.xCitations: 15 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume32, Issue3March 1968Pages 567-574 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 1 p. 136-144 Free Access THE EFFECTS OF PROSTAGLANDINS E1 AND E2 ON THE SMOOTH MUSCLE OF THE DOG SPLEEN AND ON ITS RESPONSES TO CATECHOLAMINES, ANGIOTENSIN AND NERVE STIMULATION B. N. DAVIES, B. N. DAVIES Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this authorP. G. WITHRINGTON, P. G. WITHRINGTON Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this author B. N. DAVIES, B. N. DAVIES Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this authorP. G. WITHRINGTON, P. G. WITHRINGTON Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this author First published: January 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00437.xCitations: 19AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume32, Issue1January 1968Pages 136-144 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 3 p. 483-492 Free Access EFFECT OF MERCURY DERIVATIVES, IMPLANTED INTO THE HYPOTHALAMUS, ON THE WATER INTAKE OF ALBINO RATS F. BERGMANN, F. BERGMANN Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this authorM. CHAIMOVITZ, M. CHAIMOVITZ Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this authorY. GUTMAN, Y. GUTMAN Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this authorA. ZERACHIA, A. ZERACHIA Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this author F. BERGMANN, F. BERGMANN Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this authorM. CHAIMOVITZ, M. CHAIMOVITZ Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this authorY. GUTMAN, Y. GUTMAN Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this authorA. ZERACHIA, A. ZERACHIA Department of Pharmacology, Hebrew University—Hadassah Medical School, Jerusalem, IsraelSearch for more papers by this author First published: March 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00449.xCitations: 7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References Bauer, J. & Aschner, B. (1924). Die therapeutische Wirkung des Novasurols bei Diabetes insipidus. Zentbl. inn. Med., 45, 682–688. Bergmann, F., Chaimovitz, M., Costin, A., Gutman, Y. & Ginath, Y. (1967). Water intake of rats after implantation of ouabain into the hypothalamus. Am. J. Physiol., 213, 328–332. Bergmann, F., Zerachia, A., Chaimovitz, M. & Gutman, Y. (1968). Influence of drugs, implanted into the hypothalamus, on the water consumption of rats. J. Pharmac. exp. Ther., 159, 222–232. Clarkson, T. W., Rothstein, A. & Sutherland, R. (1965). The mechanism of action of mercurial derivatives in rats. The metabolism of 203Hg-labelled chlormerodrin. Br. J. Pharmac. Chemother., 24, 1–13. Duggan, D. E. & Noll, R. M. (1965). Effects of ethacrynic acid and cardiac glycosides upon a membrane ATPase of renal cortex. Archs. Biochem. Biophys., 109, 388–396. Gussin, R. Z. & Cafruny, E. J. (1965). Effects of ethacrynic acid on renal uptake of mercury. J. Pharmac. exp. Ther., 149, 1–6. Gutman, Y. & Chaimovitz, M. (1966). Effect of chlorothiazide on water consumption in the rat. Nature Lond., 209, 410–411. Havard, C. W. H. & Wood, P. H. N. (1961). Effect of diuretics on renal water excretion in diabetes insipidus. Clin. Sci., 21, 321–332. Heinemann, H. O. & Becker, E. L. (1958). Effect of a mercurial diuretic on the excretion of “free water” in diabetes insipidus. J. appl. Physiol., 12, 51–54. Hughes, W. L. (1947). An albumin fraction isolated from human plasma as a crystalline mercuric salt. J. Am. chem. Soc., 69, 1836–1837. Jones, V. D., Lockett, G. & Landon, E. J. (1965). A cellular action of mercurial diuretics. J. Pharmac. exp. Ther., 147, 23–31. Landon, E. J. & Norris, J. L. (1963). Sodium and potassium-dependent adenosine triphosphatase activity in a rat-kidney endoplasmic reticulum fraction. Biochim. Biophys. Acta, 71, 266–276. Levy, R. I., Weiner, I. M. & Mudge, G. H. (1958). The effect of acid-base balance on the diuresis produced by organic and inorganic mercurials. J. clin. Invest., 37, 1016–1023. Massopust, L. C. (1961). In Electrical Stimulation of the Brain, ed. D. E. Sheer, pp. 182–202. Austin, Texas: Univ. Texas Press. Miller, T. B. & Riggs, D. S. (1961). Mercurial diuresis in dogs with diabetes insipidus. J. Pharmac. exp. Ther., 132, 329–338. Montemurro, D. G. & Stevenson, J. A. F. (1957). Adipsia produced by hypothalamic lesions in the rat. Can. J. Biochem. Physiol., 35, 31–37. Skou, J. C. (1965). Enzymatic basis for active transport of Na+ and K+ across cell membrane. Physiol. Rev., 45, 596–617. Taylor, C. B. (1963). The effect of mercurial diuretics on adenosine triphosphatase of rabbit kidney. in vitro IBiochem. Pharmac., 12, 539–550. Citing Literature Volume32, Issue3March 1968Pages 483-492 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 1 p. 46-56 Free Access CATECHOLAMINE AND ACETYLCHOLINESTERASE DISTRIBUTION IN RELATION TO NORADRENALINE RELEASE. AN ENZYME HISTOCHEMICAL AND AUTORADIOGRAPHIC STUDY ON THE INNERVATION OF THE CAT NICTITATING MUSCLE A. C. ESTERHUIZEN, A. C. ESTERHUIZEN Departments of Anatomy and Pharmacology, University of Wales, Cardiff Department of Physiology, University of Stellenbosch, South Africa.Search for more papers by this authorJ. D. P. GRAHAM, J. D. P. GRAHAM Departments of Anatomy and Pharmacology, University of Wales, CardiffSearch for more papers by this authorJ. D. LEVER, J. D. LEVER Departments of Anatomy and Pharmacology, University of Wales, CardiffSearch for more papers by this authorT. L. B. SPRIGGS, T. L. B. SPRIGGS Departments of Anatomy and Pharmacology, University of Wales, CardiffSearch for more papers by this author A. C. ESTERHUIZEN, A. C. ESTERHUIZEN Departments of Anatomy and Pharmacology, University of Wales, Cardiff Department of Physiology, University of Stellenbosch, South Africa.Search for more papers by this authorJ. D. P. GRAHAM, J. D. P. GRAHAM Departments of Anatomy and Pharmacology, University of Wales, CardiffSearch for more papers by this authorJ. D. LEVER, J. D. LEVER Departments of Anatomy and Pharmacology, University of Wales, CardiffSearch for more papers by this authorT. L. B. SPRIGGS, T. L. B. SPRIGGS Departments of Anatomy and Pharmacology, University of Wales, CardiffSearch for more papers by this author First published: January 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00428.xCitations: 20 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References Acheson, G. H. (1938). The topographical anatomy of the smooth muscle of the cat's nictitating membrane. Anat. Rec., 71, 297– 309. Bayliss, B. J. & Todrick, A. (1956). The use of selective acetylcholinesterase inhibitors in the estimation. of pseudocholinesterase activity in rat brain. Biochem. J., 62, 62– 67. Burgen, A. S. V. & Chipman, L. M. (1951). Cholinesterase and succinic dehydrogenase in the central nervous system of the dog. J. Physiol., Lond., 114, 296– 305. Burn, J. H. & Philpot, F. J. (1953). Effect of sympathetic denervation on the cholinesterase in the nictitating membrane and the iris. Br. J. Pharmac. Chemother., 8, 248– 251. Burn, J. H. & Rand, M. J. (1959). Sympathetic postganglionic mechanism. Nature, Lond., 184, 163– 165. Burn, J. H. & Rand, M. J. (1965). Acetylcholine in adrenergic transmission. A. Rev. Pharmac., 5, 163– 182. Burn, J. H., Rand, M. J., & Wien, R. (1963). The adrenergic mechanism in the nictitating membrane. Br. J. Pharmac. Chemother., 20, 83– 94. Cavanagh, J. B. & Holland, P. (1961). Localization of cholinesterases in the chicken nervous system and the problem of the selective neurotoxicity of organophosphorus compounds. Br. J. Pharmac. Chemother., 16, 218– 230. Feldberg, W. & Vogt, M. (1948). Acetylcholine synthesis in different regions of the central nervous system. J. Physiol., Lond., 107, 372– 381. Fray, R., Jr. & Leaders, F. E. (1967). Demonstration of separate adrenergic and cholinergic fibres to the vessels of the rear quarters of the rat by hemicholinium and a proposed role in peripheral vascular regulation. Br. J. Pharmac. Chemother., 30, 265– 273. Gardiner, J. E., Hellmann, K. & Thompson, J. W. (1962). The nature of the innervation of the smooth muscle, Harderian gland and blood vessels of the cat's nictitating membrane. J. Physiol., Lond., 163, 436– 456. Gardiner, J. E. & Thompson, J. W. (1961). Lack of evidence for a cholinergic mechanism in sympathetic transmission. Nature, Lond., 191, 86. Gerebtzoff, M. A. (1959). Cholinesterases. A histochemical contribution to the solution of some functional problems, pp. 137– 139. London: Pergamon Press. Jacobowitz, D. & Koelle, G. B. (1965). Histochemical correlations of acetylcholinesterase and catecholamines in postganglionic autonomic nerves of the cat, rabbit and guinea pig. J. Pharmac. exp. Ther., 148, 225– 237. Langley, J. N. (1895). Note on regeneration of preganglionic fibres of the sympathetic. J. Physiol., Lond., 18, 280– 284. Langley, J. N. (1900). The sympathetic and other related systems of nerves. in Text-book of Physiology, ed. E. A. Schafer, pp. 616– 625. Edinburgh and London: Young J. Pentland. Lever, J. D. & Graham, J. D. P. (1964). Nerve terminals in the nictitating membrane and in relation to pancreatic arterioles: a comparison by electron microscopy. J. Anat., 98, 473– 474. Lever, J. D., Graham, J. D. P., Irvine, G. & Chick, Wendy J. (1965). The vesiculated axons in relation to arteriolar smooth muscle in the pancreas. A fine-structural and quantitative study. J. Anat., 99, 299– 313. Lever, J. D., Spriggs, T. L. B. & Graham, J. D. P. (1967). A formol-fluorescence, fine-structural and autoradiographic study of the adrenergic innervation of the vascular tree in the intact and sympathectomized pancreas of the cat. J. Anat., in the Press. Lewis, P. R. & Shute, C. C. D. (1966). The distribution of cholinesterase in cholinergic neurons demonstrated with the electron microscope. J. Cell Sci., 1, 381– 390. Macintosh, F. C. (1941). The distribution of acetylcholine in the peripheral and the central nervous system. J. Physiol., Lond., 99, 436– 442. McEwen, L. M. (1956). The effect on the isolated rabbit heart of vagal stimulation and its modification by cocaine, hexamethonium and ouabain. J. Physiol., Lond., 131, 678– 689. Nachmansohn, D. (1959). Chemical and molecular basis of nerve activity. New York and London: Academic Press. Reynolds, E. S. (1963). The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J. biophys. biochem. Cytol., 17, 208– 212. Rosenblueth, A. & Bard, P. (1932). The innervation and functions of the nictitating membrane in the cat. Am. J. Physiol., 100, 537– 544. Spriggs, T. L. B., Lever, J. D. & Graham, J. D. P. (1967). Membrane connections at adrenergic terminals. J. Microsc., 6, 425– 430. Spriggs, T. L. B., Lever, J. D., Rees, P. M. & Graham, J. D. P. (1966). Controlled formaldehyde-catecholamine condensation in cryostat sections to show adrenergic nerves by fluorescence. Stain Technol., 41, 323– 327. Thompson, J. W. (1961). The nerve supply to the nictitating membrane of the cat. J. Anat., 95, 371– 385. Wilson, H. & Long, J. P. (1959). The effect of hemicholinium (HC-3) at various peripheral cholinergic transmitting sites. Archs int. Pharmacodyn. Ther., 120, 343– 352. Zernick, H. (1928). Zur Anatomie und Nervenphysiologie der Nickhaut des Katzenauges. Pflügers Arch. ges. Physiol., 220, 738– 759. Citing Literature Volume32, Issue1January 1968Pages 46-56 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 33, Issue 2 p. 312-318 Free Access COMPARISON OF TISSUE FLUID AND PLASMA CONCENTRATIONS OF A PROTEIN-BOUND DRUG SULPHORMETHOXINE BY IN VIVO DIALYSIS IN RATS E. G. McQUEEN, E. G. McQUEEN Department of Pharmacology and Pharmacy, University of Otago, Dunedin, New ZealandSearch for more papers by this author E. G. McQUEEN, E. G. McQUEEN Department of Pharmacology and Pharmacy, University of Otago, Dunedin, New ZealandSearch for more papers by this author First published: June 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00992.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume33, Issue2June 1968Pages 312-318 ReferencesRelatedInformation
The metabolism of phenacetin and N‐acetyl‐p‐aminophenol (APAP) was investigated in con;unction with studies of renal tubular cell excretion. A significant increase in renal tubular cell excretion was observed in 2 of 9 healthy volunteers receiving a total of 13.5 Gm. of phenacetin in 5 days and in 1 of 8 volunteers receiving the same dose of APAP. Following oral doses of 1.8 Gm., the maximum plasma concentrations of phenacetin varied from 1.3 to 24.8 P,g per milliliter, and there were often marked differences in the same individual during repeated studies. There was less variation in the plasma concentrations of free AP AP following administration of phenacetin or AP AP and the half‐life of both drugs in the plasma was relatively constant in a given individual. Approximately 78 per cent of the dose of phenacetin and 85 per cent of the APAP was recovered as free and con;ugated APAP in the urine in 24 hours. Many pigmented bands were observed on thin layer chromatograms of hydrolyzed urine extracts from sub;ects receiving phenacetin. In contrast, negligible amounts of pigment were present when APAP was taken. It was not possible to demonstrate differences in the absorption, excretion, or metabolism of phenacetin or AP AP in volunteers showing a marked renal tubular cell response compared with those who did not.
1. The changes in blood pressure in response to parenteral administration of bombesin, the active tetradecapeptide of the skin of the European discoglossid frogs Bombina bombina and Bombina variegata variegata have been investigated in some experimental animals.2. In most species, the polypeptide elicited hypertension which was usually gradual in onset and slow to disappear. Blood pressure increases rarely exceeded 40-50 mmHg. At the beginning of an experiment some dose-response relationship could often be observed, but later tachyphylaxis developed. During an intravenous infusion of bombesin the rise in blood pressure could sometimes be maintained at a steady level as long as the infusion was continued, but at other times, the rise of pressure slowly subsided with continued administration of the polypeptide. In the rat and the chicken hypertension elicited by high doses of bombesin was often followed by secondary hypotension.3. Bombesin-induced hypertension was apparently not affected by pretreatment with either alpha- or beta-adrenergic blocking agents. Similarly secondary hypotension was not abolished by atropine. Thus, the effect of bombesin on vascular smooth muscle seems to be predominantly a direct one.4. Angiotensin was usually more potent than bombesin, and its effect on blood pressure was more rapid and of shorter duration. Tachyphylaxis to angiotensin was lacking or moderate.5. In sharp contrast to the other species, the monkey responded to bombesin with frank hypotension, which was usually proportional to the dose. In the monkey the hypotensive effect of bombesin was equal to, or greater than that of eledoisin or physalaemin and bombesin-induced hypotension was of longer duration than that of the other polypeptides. Tachyphylaxis was moderate for low and adequately spaced doses of the polypeptide, but prompt and intense for high doses. Long-lasting hypotension was obtained by intravenous infusion of bombesin, but repeated infusions caused tachyphylaxis. Bombesin-induced hypotension was not affected by pretreatment with atropine.6. Bombesin may be easily distinguished from all other known peptides active on vascular and extravascular smooth muscle by its effects on blood pressure. This does not apply to bombesin-like peptides, such as alytesin and ranatensin.
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 3 p. 466-472 Free Access THE PRESENCE OF β-ADRENERGIC RECEPTORS IN THE HEPATIC VASCULATURE AIDA GEUMEI, AIDA GEUMEI Department of Pharmacology, Faculty of Medicine, Alexandria University, Egypt, U.A.R.Search for more papers by this authorMOHAMED MAHFOUZ, MOHAMED MAHFOUZ Department of Pharmacology, Faculty of Medicine, Alexandria University, Egypt, U.A.R.Search for more papers by this author AIDA GEUMEI, AIDA GEUMEI Department of Pharmacology, Faculty of Medicine, Alexandria University, Egypt, U.A.R.Search for more papers by this authorMOHAMED MAHFOUZ, MOHAMED MAHFOUZ Department of Pharmacology, Faculty of Medicine, Alexandria University, Egypt, U.A.R.Search for more papers by this author First published: March 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00447.xCitations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume32, Issue3March 1968Pages 466-472 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 32, Issue 1 p. 127-135 Free Access THE OCCURRENCE OF PROSTAGLANDIN E2 IN SPLENIC VENOUS BLOOD OF THE DOG FOLLOWING SPLENIC NERVE STIMULATION B. N. DAVIES, B. N. DAVIES Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this authorE. W. HORTON, E. W. HORTON Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1 Department of Pharmacology, The School of Pharmacy, University of London, Brunswick Square, London, W.C.1.Search for more papers by this authorP. G. WITHRINGTON, P. G. WITHRINGTON Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this author B. N. DAVIES, B. N. DAVIES Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this authorE. W. HORTON, E. W. HORTON Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1 Department of Pharmacology, The School of Pharmacy, University of London, Brunswick Square, London, W.C.1.Search for more papers by this authorP. G. WITHRINGTON, P. G. WITHRINGTON Department of Physiology, Medical College of St. Bartholomew's Hospital, Charterhouse Square, London, E.C.1Search for more papers by this author First published: January 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00436.xCitations: 66 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References Bergström, S. & Samuelsson, B. (1965). Prostaglandins. A. Rev. Biochem., 34, 101–108. Bergström, S. & Samuelsson, B. (1967). Proc. 2nd Nobel Symposium, Stockholm, 1966. Davies, B. N., Horton, E. W. & Withrington, P. G. (1967). The occurrence of prostaglandin E2 in splenic venous blood of the dog following splenic nerve stimulation. J. Physiol., Lond., 188, 38–39P. Davies, B. N. & Withrington, P. G. (1968). The effects of prostaglandins E1 and E2 on the smooth muscle of the dog spleen and on its responses to catecholamines, angiotensin and nerve stimulation. Br. J. Pharmac. Chemother., 32, 136–144. Gréen, K. & Samuelsson, B. (1964). Thin layer chromatography of prostaglandins. J. Lipid Res., 5, 117–120. Hamberg, M. & Samuelsson, B. (1966). Prostaglandins in human seminal plasma. J. biol. Chem., 241, 257–263. Holmes, S. W. & Horton, E. W. (1967). The nature and distribution of prostaglandins in the central nervous system of the dog. J. Physiol., Lond., 191, 134–135P. Holmes, S. W., Horton, E. W. & Main, I. H. M. (1963). The effect of prostaglandin E1 on responses of smooth muscle to catecholamines, angiotensin and vasopressin. Br. J. Pharmac. Chemother., 21, 538–543. Horton, E. W. & Main, I. H. M. (1967). The identification of prostaglandins in central nervous tissues of the cat and the chicken. Br. J. Pharmac. Chemother., 30, 582–602. Ramwell, P. W. & Shaw, J. E. (1966). Spontaneous and evoked release of prostaglandins from cerebral cortex of anaesthetized cats. Am. J. Physiol., 211, 125–133. Ramwell, P. W., Shaw, J. E., Douglas, W. W. & Poisner, A. M. (1966). Efflux of prostaglandin from adrenal glands stimulated with acetylcholine. Nature, Lond., 210, 273–274. Ramwell, P. W., Shaw, J. E. & Kucharski, J. (1965). Prostaglandin: release from the rat phrenic nerve diaphragm preparation. Science, 149, 1390–1391. Shaw, J. E. (1966). Prostaglandin release from adipose tissue “in vitro” evoked by nerve stimulation or catecholamines. Fedn Proc., 25, 770. Citing Literature Volume32, Issue1January 1968Pages 127-135 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 33, Issue 3 p. 544-551 Free Access TEMPERATURE EFFECTS AND CATALEPSY PRODUCED BY MORPHINE INJECTED INTO THE CEREBRAL VENTRICLES OF RABBITS U. BANERJEE, U. BANERJEE National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this authorT. F. BURKS, T. F. BURKS National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this authorW. FELDBERG, W. FELDBERG National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this authorCECILIE A. GOODRICH, CECILIE A. GOODRICH National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this author U. BANERJEE, U. BANERJEE National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this authorT. F. BURKS, T. F. BURKS National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this authorW. FELDBERG, W. FELDBERG National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this authorCECILIE A. GOODRICH, CECILIE A. GOODRICH National Institute for Medical Research, Mill Hill, London N.W.7Search for more papers by this author First published: July 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00503.xCitations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume33, Issue3July 1968Pages 544-551 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 33, Issue 3 p. 531-536 Free Access THE ACTION OF PHYSOSTIGMINE AND THE DISTRIBUTION OF CHOLINESTERASES IN THE CHICKEN OESOPHAGUS A. L. BARTLET, A. L. BARTLET Department of Veterinary Pharmacology, Royal (Dick) School of Veterinary Studies, EdinburghSearch for more papers by this authorT. HASSAN, T. HASSAN Department of Veterinary Pharmacology, Royal (Dick) School of Veterinary Studies, EdinburghSearch for more papers by this author A. L. BARTLET, A. L. BARTLET Department of Veterinary Pharmacology, Royal (Dick) School of Veterinary Studies, EdinburghSearch for more papers by this authorT. HASSAN, T. HASSAN Department of Veterinary Pharmacology, Royal (Dick) School of Veterinary Studies, EdinburghSearch for more papers by this author First published: July 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00501.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References Bartlet, A. L. (1968a). The effect of vagal stimulation and eserine on isolated guinea-pig oesophagus. Q. Jl exp. Physiol., 53, 170– 174. Bartlet, A. L. (1968b). An atypical action of acetylcholine on the striped muscle of the guinea-pig oesophagus. Q. Jl exp. Physiol., 53, 175– 180. Bartlet, A. L. & Hassan, T. (1968). Some actions of histamine and 5-hydroxytryptamine on isolated chicken oesophagus. Br. J. Pharmac. Chemother., 32, 156– 163. Burn, J. H. & Rand, M. J. (1960). The relation of circulating noradrenaline to the effect of sympathetic stimulation. J. Physiol., Lond., 150, 295– 305. Calhoun, M. L. (1933). The microscopic anatomy of the digestive tract of Gallus domesticus. Iowa State Coll. J. Sci., 7, 261– 381. Calhoun, M. L. (1954). Microscopic Anatomy of the Digestive System of the Chicken. Ames, Iowa: Iowa State Press. Cuthbert, A. W. (1963). An acetylcholine-like substance and cholinesterase in the smooth muscle of the chick amnion. J. Physiol., Lond., 166, 284– 295. Krebs, H. A. & Henseleit, K. (1932). Untersuchungen über die Harnstoffbildung im Tierkörper. Hoppe-Seyler's Z. physiol. Chem., 210, 33– 66. Krnjević, K. & Silver, A. (1965). A histochemical study of cholinergic fibres in the cerebral cortex. J. Anat., 99, 711– 759. Citing Literature Volume33, Issue3July 1968Pages 531-536 ReferencesRelatedInformation
British Journal of Pharmacology and ChemotherapyVolume 33, Issue 3 p. 480-492 Free Access 5-HYDROXYTRYPTAMINE RECEPTORS IN THE MOUSE DUODENUM ANNA B. DRAKONTIDES, ANNA B. DRAKONTIDES Department of Anatomy, Cornell Medical College, New York, New YorkSearch for more papers by this authorM. D. GERSHON, M. D. GERSHON Department of Anatomy, Cornell Medical College, New York, New YorkSearch for more papers by this author ANNA B. DRAKONTIDES, ANNA B. DRAKONTIDES Department of Anatomy, Cornell Medical College, New York, New YorkSearch for more papers by this authorM. D. GERSHON, M. D. GERSHON Department of Anatomy, Cornell Medical College, New York, New YorkSearch for more papers by this author First published: July 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00496.xCitations: 41AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Ambache, N. (1951). Unmasking, after cholinergic paralysis by botulinum toxin, of a reversed action of nicotine on the mammalian intestine, revealing the probable presence of local inhibitory ganglion cells in the enteric plexuses. Br. J. Pharmac. Chemother., 6, 51– 67. Bennett, M. R. (1966). Rebound excitation of the smooth muscle cells of the guinea-pig taenia coli after stimulation of intramural inhibitory nerves. J. Physiol., Lond., 185, 124– 131. Boyd, H., Burnstock, G., Campbell, G., Jowett, A., O'Shea, J. & Wood, M. (1963). The cholinergic blocking action of adrenergic blocking agents in the pharmacological analysis of autonomic innervation. Br. J. Pharmac. Chemother., 20, 418– 435. Brownlee, G. & Johnson, E. S. (1963). The site of the 5-hydroxytryptamine receptor on the intramural nervous plexus of the guinea-pig isolated ileum. Br. J. Pharmac. Chemother., 21, 306– 322. Bülbring, E. (1953). Measurements of oxygen consumption in smooth muscle. J. Physiol., Lond., 122, 111– 134. Bülbring, E. & Gershon, M. D. (1968). 5-Hydroxytryptamine participation in the vagal inhibitory innervation of the stomach. J. Physiol., Lond., 192, 823– 846. Bülbring, E. & Tomita, T. (1967). Properties of the inhibitory potential of smooth muscle as observed in the response to field stimulation of the guinea-pig taenia coli. J. Physiol., Lond., 189, 299– 315. Burnstock, G., Campbell, G. & Rand, M. J. (1966). The inhibitory innervation of the taenia of the guinea-pig caecum. J. Physiol., Lond., 182, 504– 526. Day, M. & Vane, J. R. (1963). An analysis of the direct and indirect actions of drugs on the isolated guinea-pig ileum. Br. J. Pharmac. Chemother., 20, 150– 170. Erspamer, V. (1966). Peripheral physiological and pharmacological actions of indolealkylamines. In Handbuch der experimentellen Pharmakologie. XIX, 5-Hydroxytryptamine and Related Indolealkylamines, ed. V. Erspamer, pp. 298– 311. Berlin, Heidelberg, New York: Springer-Verlag. Fastier, F. N., McDowall, M. A. & Waal, H. (1959). Pharmacological properties of phenyldiguanide and other derivatives in relation to those of 5-HT. Br. J. Pharmac. Chemother., 14, 527– 535. Gaddum, J. H. & Picarelli, Z. P. (1957). Two kinds of tryptamine receptor. Br. J. Pharmac. Chemother., 12, 323– 328. Garattini, S. & Valzelli, L. (1965). Serotonin, pp. 242– 276. Amsterdam, London, New York: Elsevier Publishing Co. Gershon, M. D. (1967). Effects of tetrodotoxin on innervated smooth muscle preparations. Br. J. Pharmac. Chemother., 29, 259– 279. Gyermek, L. (1966). Drugs which antagonize 5-hydroxytryptamine and related indolealkylamines. In Handbuch der experimentellen Pharmakologie. XIX. 5-Hydroxytryptamine and Related Indolealkylamines, ed. V. Erspamer, pp. 471– 528. Berlin, Heidelberg, New York: Springer-Verlag. Iversen, L. L. (1963). Uptake of noradrenaline by isolated perfused rat heart. Br. J. Pharmac. Chemother., 21, 523– 537. Kuriyama, H., Osa, T. & Toida, N. (1966). Effects of tetrodotoxin on smooth muscle cells of guinea-pig taenia coli. Br. J. Pharmac. Chemother., 27, 366– 376. Nickerson, M. (1949). The pharmacology of adrenergic blockade. Pharmac. Rev., 1, 27– 101. Paton, W. D. M. (1955). The response of the guinea-pig ileum to electrical stimulation by coaxial electrodes. J. Physiol., Lond., 127, 40– 41. Paton, W. D. M. (1957a). The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum. Br. J. Pharmac. Chemother., 12, 119– 127. Paton, W. D. M. (1957b). Histamine release by compounds of simple chemical structure. Pharmac. Rev., 9, 269– 328. Paton, W. D. M. & Perry, W. L. M. (1953). The relationship between depolarization and block in the cat's superior cervical ganglion. J. Physiol., Lond., 119, 43– 57. Toida, N. & Osa, T. (1965). Spike generating mechanism of smooth muscle cell membrane. Abst. XIII Int. Cong. Physiol. Sci., Tokyo, p. 94. Trendelenburg, U. (1957). Reaktion sympathischer Ganglien wahrend der Ganglienblockade durch Nicotin. Arch. exp. Path. Phormak., 230, 448– 456. Citing Literature Volume33, Issue3July 1968Pages 480-492 ReferencesRelatedInformation
