1.Changing from an iso- to a hyposmotic medium (in which 25% of the NaCl was omitted) caused a transient increase in the frequency of the spontaneous spike activity of leech ganglion cells, followed by a decrease of responsiveness.2.Addition of 3 × 10−5 g./ml. of adrenaline caused a transient increase in the rate of spontaneous discharges of Retzius nerve cells of a leech equilibrated in a hyposmotic medium. This was partially blocked by propranolol (10−4 g./ml.).3.A small drop in the input resistance was observed in adrenaline leech saline.4.Tentative explanations for the site of action of adrenaline are proposed.
1.3-Trifluormethyl-4-nitrophenol (TFM), at a concentration of 10.0 mg./l., caused a significant reduction in oxygen consumption by homogenates of rainbow trout brain and the livers of white sucker, rainbow trout, largemouth bass, and bluegill sunfish.2.Largemouth bass and white sucker livers were most sensitive, showing significant reduction in oxygen utilization also at 1·0 mg./l. TFM.3.In the presence of 1·0 mg./l. TFM, the rate of respiration by trout brain increased significantly, but at 0·5 mg./l. TFM there was no significant change in respiration rate.4.No significant biotransformation of TFM occurred in trout brain homogenates, but all other fish tissues produced at least two TFM metabolites when exposed to 1·0 or 10·0 mg./l. [14C]TFM.
The depolarizing potency of the following three homological series: ‘BTM’: Me3N(CH2)nNMe3, n = 9–16; ‘D’: Me3NCH2CH2OCO(CH2)mCOOCH2CH2NMe3, m = 1–8; ‘D-mono’: Me3NCH2CH2OCO(CH2)mCOOCH2CH2H, m = 2–8, was compared by means of intracellular microelectrodes on identified giant neurons of the small parietal ganglion of Limnaea stagnalis after irreversible inhibition of cholinesterases. The equipotent molar ratio of the corresponding members of the series D : D-mono : BTM was approximately 1 : 3 : 10. These results indicate the important role of the ester groups in the depolarizing action of the quaternary and bisquaternary compounds as well as the importance of the second cationic head in series D. At variance with all other members of the D-series, suxamethonium (D-2) is not more active than decamethonium (BTM-10) and less potent than D-2-mono. The second cationic head reduces the depolarizing action of suxamethonium on the neurons studied. The study of some derivatives of the D-mono series had shown that replacing of the ‘second’ (more remote from the nitrogen) ester group by two methylene groups strongly reduces the depolarizing activity but the ‘reversal’ of the second ester group (that is the transposition of the ether oxygen and the carbonyl group) does not change the activity. The contribution of the second ester group in the interaction of the members of the D-mono series with the cholinoceptive membrane is discussed.
1.The striated musculature of the vas deferens of the crayfish responds to l-glutamate with a contraction.2.The action of l-glutamate is reduced or abolished by Na-free saline. It is usually enhanced by picrotoxin (PTX) and is greatly augmented by media of low Cl concentration, even in the absence of external Na. This augmentation is blocked by PTX.3.GABA either causes contraction or does not; in the latter case it inhibits the contraction caused by l-glutamate. In low Cl media GABA always causes a strong contraction; like its inhibitory action this is blocked by PTX.4.It is suggested that GABA activates Cl channels and that l-glutamate activates Na and Cl channels. Cl activation, whether caused by GABA or by l-glutamate, is blocked by PTX.5.Since PTX does not interfere with Na activation, it is likely that the receptors responding with Cl activation are different from those responsible for Na activation and that the receptors responding to GABA can also be activated by l-glutamate.
1.Acetylcholine (ACh), added into the 39° C incubation medium in concentrations up to 2 × 10−3g. per ml., prolonged the thermal resistance of ciliary activity in the isolated gills of the freshwater mussel, Anodonta cygnea cellensis, acclimated for 1 day to cold or warm temperature in tap water or in cholinomimetic or anticholinergic solution.2.Atropine and eserine added into the acclimation medium reduced the higher thermal resistance of the warm-acclimated gills to the level of the cold-acclimated controls, but had no effect on the cold-acclimated gills in the water incubation at 39° C.3.Tetramethylammonium (TMA) added into the acclimation medium reduced the thermal resistance measured in the 39° C water incubation of the isolated gills acclimated either to cold or warm conditions.4.Equimolar doses of ACh, choline and TMA in the incubation medium at 39° C enhanced in equal degree the thermal resistance of ciliary activity in the cold-acclimated as well as in the warm-acclimated gills.5.It is suggested that the thermal resistance of ciliary activity in the Anodonta gills is regulated by cholinergic mechanism. The functional basis of the thermal resistance acclimation may be the ACh receptor molecule synthesis dependent on the external temperature.
1.The toxicity and action of fluenethyl or 2-fluoroethyl(4-biphenylyl) acetate, several other monofluoroethyl esters, monofluoroethanol, monofluoroacetic acid and fluoroacetamide were studied in mice, houseflies (Musca domestica L.) and twospotted spider mites (Tetranychus urticae Koch).2.Toxicity varied markedly with the test compound, method of application and biological species. Generally, monofluoroacetic acid, monofluoroethanol and fluenethyl were the most active materials examined. Intoxicated mice and houseflies exhibited classic symptoms of organofluorine poisoning; spider mites exhibited a brief period of hyperactivity.3.Ethanol, isoniazid, triazole, acetamide, sodium acetate and monoacetin afforded some protection against the toxicity of fluenethyl and monofluoroethanol to mice, suggesting that metabolic transformation of these two fluorine-containing compounds was essential for toxicity.4.Mice, houseflies and spider mites poisoned with fluenethyl and other fluorine-containing compounds accumulated high levels of citrate as compared to controls, providing evidence that aconitase or citrate (isocitrate) hydrolyase (E.C. 4.2.1.3) was attacked.5.It was concluded that the monofluoroethanol released upon esteratic cleavage of fluenethyl was oxidized to monofluoroacetic acid which, after conversion to fluorocitrate, inhibited aconitase. This appeared to be the mechanism for the toxic action of fluenethyl and the other monofluoroethyl esters in the mouse, housefly, and twospotted spider mite.
1.The therapeutic action of an anticomplementary agent, fumaropimaric Acid (FMP), was investigated in experimental immune nephritis.2.Nephrotoxic glomerulonephritis of variable severity was produced in rats with intravenous antiglomerular antiserum. Four to 20 hours later 51Cr. EDTA clearances, protein excretion and urinary flow rates were studied by ureteric catheterization during mannitol diuresis.3.The action of FMP was assessed under these conditions. It was intravenously infused and serial changes in renal function in 15 nephritic and 5 control animals analysed.4.Four of the nephritic group showed a degree of improvement related to the treatment period. Seven animals responded with statistically insignificant improvement in renal function.5.Histological examination suggested that FMP may have reduced the number of polymorphonuclear leucocytes in the nephritic glomeruli.
1.The properties of sarcolemmal preparations of Na+,K+-stimulated ATPase from normal and denervated rabbit muscles were compared.2.The value of ATPase activity from denervated muscles was higher than that from normal ones, but the pH and Na+/K+ ratio dependence as well as the relation of activities of Na+,K+-ATPase and Mg2+-ATPase were the same in both cases.3.At the same time Na+,K+-ATPase from denervated muscles was more sensitive toward acetylcholine (ACh) (Ki = 0.5 × 10−5M), than that from normal ones (Ki = 10.0 × 10−5M).4.It is possible that some of the properties of denervated muscles may at least be concerned with increasing the activity and ACh sensitivity of Na+,K+-ATPase of their membranes.
1.Biphenyl was metabolized in vitro to 4-hydroxybiphenyl and, to a lesser extent, 2-hydroxybiphenyl by tissues of Raja ocellata, Salvelinus fontinalis, Homarus americanus, Gerydon quinquidens, Cancer irroratus, Mytilus edulis, Asterias vulgaris and by zooplankton.2.Rates of 4-hydroxybiphenyl production ranged from 400 nmoles per g. tissue per hour in Raja ocellata to approximately 2 nmoles per g. tissue per hour in Asterias vulgaris, and were generally considerably slower than reported in the literature for several terrestrial species.
5-Hydroxytryptamine (5-HT, serotonin) is present in the eyestalks (7.38–7.63 μg./g. wet weight) and brain (2.77–3.38 μg./g. wet weight) of the fiddler crab Uca pugilator. Reserpine and 5,6-dihydroxytryptamine produced a decrease in the 5-HT levels of both the eyestalks and brain. Both drugs also caused concentration of the red chromatophoric pigment. Injection of pargyline, a monoamine oxidase inhibitor, resulted in an increase in the 5-HT content of both the eyestalks and brain. This drug evoked dispersion of the red chromatophoric pigment. Bilateral eyestalk ablation resulted in an increase of the 5-HT level of the brain. These results are consistent with the hypothesis that 5-HT has a normal role in the fiddler crab as a neurotransmitter involved in stimulating the release of red pigment-dispersing hormone.
Acute exposure to cold (30 minutes at − 5°C) significantly decreased the body temperature of mice acclimated either to 32°C or to 22°C, but not of mice acclimated to 5°C. Prior injection of noradrenaline (NA) did not improve the animals' ability to withstand cold exposure. Propranolol injection induced a significant decrease of body temperature in all mouse groups. At the same time, the blood free fatty acid (FFA) level increased significantly in mice acclimated to 32°C or to 22°C. This effect was further stimulated by prior injection of NA. In cold-acclimated mice, no change in blood FFA level was measured. NA injection also had no effect. Propranolol injection lowered FFA level in all groups. Acute exposure to cold induced a rapid output of glycogen by the liver of all groups and this was further increased by injection of propranolol. Lipolytic and anti-lipolytic effects of NA and propranolol on the incubated interscapular brown adipose tissue correlated well to the lipolytic and anti-lipolytic effects seen in vivo. The oxygen consumption of the interscapular brown adipose tissue of cold-acclimated mice was significantly more effective than in warm-acclimated mice. Only in cold-acclimated mice did NA have a stimulatory effect.
1.In vivo and in vitro rates of metabolism of phenylbutazone have been studied in normal, alloxan diabetic and insulin-treated diabetic rats.2.In the in vivo experiments urine was collected periodically after an oral dose of the drug and analysed spectrophotometrically for unchanged phenylbutazone and its metabolites. Concurrently, blood specimens were also obtained and similarly analysed. The results revealed a slower metabolic rate of the drug in the diabetic animals than in the controls, which was commensurate with the severity of the diabetic state.3.The pattern of the metabolic rate of phenylbutazone incubated with microsomal preparations was essentially similar to that observed in the intact animal.4.Insulin treatment brought back the metabolic rate to near normal levels.5.It is suggested that the anomolies in the metabolism of phenylbutazone observed in the alloxan diabetic rat could be ascribed, in the main, to a deficiency in NADPH and/or in microsomal and certain other hepatic enzymes.
Anesthesia induced by tricaine methanesulfonate (MS 222), quinaldine and urethane in the rainbow trout (Salmo gairdneri) produces cardioacceleration followed by prolonged bradycardia. The response to anesthesia was investigated with suitably timed injections of atropine, dichloroisoproterenol, acetylcholine and epinephrine. Cardioacceleration was found to be due to catecholamine release caused by the stress of anesthesia, and bradycardia was found to be produced by an increase in vagal tone caused by anoxia. Telemetric studies indicate all cardiac rates return to normal in 8 hours after removal from the anesthetic. Of the three anesthetics MS 222 provided the most consistent and least harmful cardiac and respiratory side effects.
Experimental degeneration of the tract between the superior frontal and vertical lobes of the supraoesophageal ganglia in Octopus vulgaris decreased the dopamine and noradrenaline concentrations in the vertical lobe. Vertical lobes from different cephalopods showed considerable variations in their noradrenaline to dopamine ratios. The evidence suggests there are both dopaminergic and noradrenergic afferent fibres to the vertical lobe and that their relative proportions vary between different cephalopods.
The effect of intraperitoneally injected 6-hydroxydopamine on the levels of adrenaline and noradrenaline in the Taenia coli of the guinea-pig was investigated by fluorimetrical analysis of the amines and fluorescent histochemistry. Noradrenaline levels decreased significantly during the period of treatment, while the adrenaline levels were not significantly affected. Together with the decrease in noradrenaline levels, the fluorescent fibres of the Taenia coli disappeared.
This report shows the diurnal fluctuation of histamine content in blood and tissue of chickens exposed to 10 hours of darkness and 14 hours of light. Histamine determinations made at various times reveal peak levels in blood and infundibulum of the female at the onset of light and a sharp decline in histamine content of both during oviposition.
1.Cockroaches exposed to 6 atm of O2 for 1·5, 2 and 3 hours had reduced locomotor activity as measured by a tilting activity cell.2.Righting reflex was preserved in only 11% of insects in oxygen for 3 hours.3.Abdominal distension and tremor of the extremities occurred in about one-half the insects after 2 hours and in 94% of the insects after 3 hours of O2 exposure (6 atm).
In Retzius cells of leech segmental ganglia sodium phenobarbital, 0·1–10 mM, caused abnormally large excitatory post-synaptic potentials. At 1–10 mM, sodium phenobarbital caused hyperpolarization attributable to increased membrane potassium conductance.
Several tissues of two intertidal gastropod mollusks belonging to the superfamily Muricacea contained, in addition to acetylcholine, other choline esters that produced contraction of the frog rectus abdominis muscle. One major active choline ester found in acetone extracts of the hypobranchial gland of Acanthina spirata had pharmacological properties and a nuclear magnetic resonance spectrum consistent with murexine [urocanylcholine, β-[4-imidazolyl]acrylcholine). A principal active compound from the hypobranchial gland of Nucella ( = Thais) emarginata differed pharmacologically from murexine and was tentatively identified by nuclear magnetic resonance spectroscopy as the previously unreported N-methyl derivative of murexine, β-[4-(1-or 3-methyl)-imidazolyl]acrylcholine.
1.The cholinesterase inhibitor armin has a calculated LD50 of 120 μg. per kg. in the fish Serranus scriba compared to a value of 500 μg. per kg. reported for mice.2.At a dose level of 60 μg. per kg. armin caused marked depression of active avoidance behaviour in Serranus scriba up to 6 hours after injection. Recovery of responses had occurred by 24 hours.3.This same dose of armin reduced brain cholinesterase activity to 80% of control levels 2 hours after administration, with return towards normal values after 6 hours and complete recovery by 24 hours.4.Although not conclusive, the time course of the behavioural deficit and enzyme depression suggest a direct casual relationship.
