Keshavarziam, A. M.D.; Anagnostides, A. M.D.; Chadwick, V. S. M.D.; Fitzpatrick, M. L. Ph.D. Author Information

The effect of the selective antimuscarinic agent, pirenzepine, on gallbladder function was studied in six healthy volunteers, using 99mTc HIDA (N‐[2,6‐diethylthenyl] carbamoylmethyl iminodiacetic acid) hepatobiliary scanning. Pirenzepine, in doses that inhibit gastric acid secretion, did not alter gallbladder emptying responses to sham feeding stimulation or to a test meal.

Normal volunteers (n = 6), patients with untreated celiac disease and subtotal villous atrophy (n = 6), patients with nonresponsive celiac disease (n = 2), and patients with celiac disease on a gluten-free diet with a virtually normal biopsy specimen (n = 6) drank a liquid fat meal after an overnight fast. Gallbladder emptying was monitored by using 99mTc-eHIDA, and blood samples were taken for cholecystokinin estimation by radioimmunoassay after high-performance liquid chromatography. The half-times of gallbladder emptying were 20.4 +/- 2.9 min (mean +/- SEM) for normals and 22.1 +/- 2.8 min in treated patients with celiac disease (NS). In patients with untreated celiac disease half-times were 154.3 +/- 10.3 min (p less than 0.02 vs. normals and treated patients with celiac disease), and in 2 nonresponsive patients, half-times were 40.7 and 37.3 min. Integrated plasma cholecystokinin responses were 473 +/- 87 and 436 +/- 137 pmol X L-1 X 30 min-1 in normals and treated patients with celiac disease (NS). In untreated patients with celiac disease values were 16 +/- 9 pmol X L-1 X 30 min-1 (p less than 0.001 vs. normals and treated patients with celiac disease), and in nonresponsive patients values were 442 and 322 pmol X L-1 X 30 min-1. In 2 patients studied before and during gluten-free diet half-times for gallbladder emptying changed from 168.9 and 302.4 min to 20.1 and 23.4 min, and cholecystokinin responses changed from 0 and 45 to 623 and 298 pmol X L-1 X 30 min-1. Cholecystokinin immunoreactivity cochromatographing with cholecystokinin-octapeptide was responsible for 50%-60% of circulating cholecystokinin in normals and in treated patients but the small amount of cholecystokinin that was released in untreated patients with celiac disease cochromatographed with cholecystokinin-33/39. We conclude that there is a reversible defect of gallbladder emptying and cholecystokinin release in celiac disease.

A drink of water was found to cause partial emptying of the human gallbladder in parallel with the release of motilin. The water-induced effect on the gallbladder was abolished by atropine, whereas the release of motilin remained unchanged. Exogenous infusions of porcine motilin aimed at achieving either a physiological or a pharmacological plasma motilin increment were both without effect on gallbladder dynamics as compared with saline infusions. It is concluded that the water-induced gallbladder emptying is vagally dependent. Furthermore, the results suggest that motilin does not cause gallbladder emptying in man.

Neuropeptide Y (NPY) and peptide YY (PYY) are two structurally related peptides. PYY has been identified within endocrine cells and NPY within nerves of the gastrointestinal tract. Infusion of PYY at a low dose at a nominal rate of 2 pmol/kg/min resulted in an increment of 59.2 +/- 7.1 pmol/1 in plasma concentration and a significant delay in gastric emptying of glucose. Infusion of NPY at the same rate produced similar plasma concentrations (52.5 +/- 1.1 pmol/1) and had no significant effect on the rate of gastric emptying.

To establish the sensitivity of the gallbladder in relation to plasma concentrations of cholecystokinin, a dose-response study was performed in five normal volunteers. Cholecystokinin octapeptide was infused in ascending incremental dose sequence, interval blood samples taken for estimation of plasma hormone concentrations and gallbladder emptying rates monitored continuously using 99mTc-HIDA. In five other volunteers, gallbladder emptying rates following a liquid fat meal were measured. Infusion rates of 0.0, 0.75 +/- 0.2, 6.8 +/- 0.5, 23.8 +/- 1.6 and 66.1 +/- 2.5 pmol cholecystokinin kg-1 h-1 produced plasma concentrations of less than 3.0 (undetectable), less than 3.0, 6.6 +/- 1.8, 13.3 +/- 1.5 and 26.9 +/- 2.9 pmol l-1 respectively and gallbladder emptying rates (% min-1) of 0.0, 0.0, 0.14 +/- 0.15, 1.57 +/- 0.38 and 4.29 +/- 1.12. Following the fat meal, peak plasma cholecystokinin concentrations reach 30 pmol l-1 and gallbladder emptying rates (% min-1) are 3.86 +/- 1.01. We conclude that the threshold of the gallbladder to circulating cholecystokinin octapeptide is around 6 pmol l-1, but that infusions which result in plasma levels of around 25 pmol l-1 produce gallbladder emptying rates comparable with those seen after oral fat. This suggests that the gallbladder is equally sensitive to endogenous and exogenous cholecystokinin and that plasma concentrations observed after oral fat can entirely account for the gallbladder response.

Conference Abstract| September 01 1983 A Cephalic Phase of Biliary Secretion A.A. Anagnostides; A.A. Anagnostides 1Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar V.S. Chadwick; V.S. Chadwick 1Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar M.L. Fitzpatrick; M.L. Fitzpatrick 1Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar P.N. Maton P.N. Maton 1Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1983) 65 (3): 12P. https://doi.org/10.1042/cs065012Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation A.A. Anagnostides, V.S. Chadwick, M.L. Fitzpatrick, P.N. Maton; A Cephalic Phase of Biliary Secretion. Clin Sci (Lond) 1 September 1983; 65 (3): 12P. doi: https://doi.org/10.1042/cs065012Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1983 The Biochemical Society and the Medical Research Society1983 Article PDF first page preview Close Modal You do not currently have access to this content.

In 16 diabetic patients with microangiopathy, survival of 111In-labelled autologous platelets, mean platelet volume, megathrombocyte index, spontaneous and ADP-induced platelet aggregation, platelet retention, β-thromboglobulin, von Willebrand factor and factor VIII-related antigen were measured; the splenic uptake of radioactive label was quantitated in six patients. Compared with normal subjects, increased platelet aggregation (p<0.01), von Willebrand factor (p<0.02) and factor VIII-related antigen (p<0.02) were observed. Platelet survival was shortened in two patients. It correlated inversely with the splenic radioactivity uptake (r=-0.95; p<0.01), suggesting that platelets ended their life in the spleen, not in the microcirculation. No significant relationships were found between the various tests performed, nor between these and the severity of microangiopathy or other clinical data. In spite of the evidence for altered platelet function in patients with diabetic microangiopathy, currently available tests are not specific enough to clarify the nature of these changes or their possible pathogenic significance.

Exogenous intravenous infusions of control saline, somatostatin, motilin and somatostatin and motilin together were compared in normal volunteers for their effects on the rise of blood glucose following 50 g oral glucose and for their effects on gastric emptying and plasma hormone concentrations. All regulatory peptide infusions increased the rate of gastric emptying by between 182% and 198% at 60 min post-ingestion. The glucose response during the oral glucose tolerance test was suppressed when somatostatin with or without motilin was infused but was increased during motilin. The somatostatin infusion reduced concentrations of motilin, insulin, gastric inhibitory polypeptide, gastrin and neurotensin whilst the motilin infusion was associated with an increased initial rise in insulin and gastric inhibitory polypeptide. The metabolic effects of the motilin infusion were overriden by the effects of somatostatin when both peptides were infused together; this suggests that somatostatin inhibits both the effects and secretion of motilin.

Conference Abstract| February 01 1982 Plasma Motilin and Biliary Output in Man T Svenberg; T Svenberg 1Royal Postgraduate Medical School, London W12 OHS, UK Search for other works by this author on: This Site PubMed Google Scholar N D Christofides; N D Christofides 1Royal Postgraduate Medical School, London W12 OHS, UK Search for other works by this author on: This Site PubMed Google Scholar M L Fitzpatrick; M L Fitzpatrick 1Royal Postgraduate Medical School, London W12 OHS, UK Search for other works by this author on: This Site PubMed Google Scholar S R Bloom; S R Bloom 1Royal Postgraduate Medical School, London W12 OHS, UK Search for other works by this author on: This Site PubMed Google Scholar R B Welbourn R B Welbourn 1Royal Postgraduate Medical School, London W12 OHS, UK Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1982) 62 (2): 20P–21P. https://doi.org/10.1042/cs062020Pb Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation T Svenberg, N D Christofides, M L Fitzpatrick, S R Bloom, R B Welbourn; Plasma Motilin and Biliary Output in Man. Clin Sci (Lond) 1 February 1982; 62 (2): 20P–21P. doi: https://doi.org/10.1042/cs062020Pb Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1982 The Biochemical Society and the Medical Research Society1982 Article PDF first page preview Close Modal You do not currently have access to this content.

Conference Abstract| September 01 1982 Dose-Response Study of Cholecystokinin Octapeptide (CCK 8) in Man: Effects on Gallbladder Contraction and Plasma CCK 8 Concentrations P.N. Maton; P.N. Maton 1Gastroenterology Unit, Department of Medicine, Royal Postgraduate Medical School, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar A.C. Selden; A.C. Selden 1Gastroenterology Unit, Department of Medicine, Royal Postgraduate Medical School, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar M.L. Fitzpatrick; M.L. Fitzpatrick 1Gastroenterology Unit, Department of Medicine, Royal Postgraduate Medical School, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar V.S. Chadwick V.S. Chadwick 1Gastroenterology Unit, Department of Medicine, Royal Postgraduate Medical School, London W12 OHS Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1982) 63 (3): 9P. https://doi.org/10.1042/cs063009Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation P.N. Maton, A.C. Selden, M.L. Fitzpatrick, V.S. Chadwick; Dose-Response Study of Cholecystokinin Octapeptide (CCK 8) in Man: Effects on Gallbladder Contraction and Plasma CCK 8 Concentrations. Clin Sci (Lond) 1 September 1982; 63 (3): 9P. doi: https://doi.org/10.1042/cs063009Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1982 The Biochemical Society and the Medical Research Society1982 Article PDF first page preview Close Modal You do not currently have access to this content.

The fasting output of bile into the bowel was investigated in nine healthy volunteers by hepatobiliary scanning. Subjects were studied twice, on each occasion for 2.5 hours. A significant flow of radioactivity from the gall bladder to the duodenum was observed on one or two occasions during each experiment. A 32 +/- 4% mean decrease in counts over the gall bladder was recorded, indicating partial emptying of this organ in the interdigestive state. The output of bile into the bowel was found to be related to fluctuations in fasting plasma motilin levels in that a significant motilin increment (18 +/- 4 pmol/l, p less than 0.005) paralleled the appearance of radioactivity in the duodenum. The onset of gall-bladder emptying regularly preceded the peak in plasma motilin (mean: 25 +/- 2 minutes). Atropine, intravenously, 0.6 mg followed by 0.3 mg, nearly abolished both fasting biliary output and plasma motilin fluctuations. Thus, bile output appears to occur frequently in fasting humans, but our data do not allow any conclusions as to the possible causal relationship between fasting gall-bladder emptying and release of motilin. Cholinergic influences appear to be of importance in the regulation of interdigestive biliary output in man.

Using the lipophilic chelating agent, acetylacetone, red cells have been radiolabelled with the short-lived, generator-produced isotope, 113mIn. Following re-injection of these labelled cells, red cell volume has been measured and compared with corresponding values using 99mTc labelled red cells in 18 patients, and with 51Cr labelled red cells in five patients. 99mTc slightly overestimated red cell volume in relation to 113mIn, but 51Cr values were identical to 113mIn values. There was a close correlation between splenic red cell pool measured with 99mTc and with 113In. It was concluded that the intracellular stability and gamma emission of 113mIn make this isotope a superior alternative to 99mTc and 51Cr in measurements of red cell volume and splenic red cell pool.

Bovine pancreatic polypeptide (PP) was infused intravenously in 5 healthy subjects on two separate occasions with mean doses of 1 and 2 pmol kg-1 min-1, respectively, which achieved plasma levels equal to and twice those observed after a normal mixed breakfast. The gastric emptying rate of a carbohydrate-rich breakfast 20 min after the start of each PP infusion was not significantly different from a control infusion of 0.15 M saline. PP is unlikely to be an important physiological modulator of gastric emptying rate in man.

The effect of natural motilin on the rate of gastric emptying of 200 ml 25% glucose was studied in seven subjects using a 99mtechnetium tin colloid marker. On the control day the subjects received intravenous saline while on the test day they received a motilin infusion of 0.2 pmol/kg/min. Infusions were blind and given in random order. Thirty minutes after glucose ingestion, 25.5 +/- 2% of the isotope had emptied during motilin infusion, compared with 11.0 +/- 1.5% with saline (p < 0.005). Plasma motilin concentrations rose from a basal value of 23 +/- 5 pM to 57 +/- 9 pM during the motilin infusion. The faster emptying rates after motilin were reflected in a faster rise of plasma glucose and insulin. The rate of emptying of 99mtechnetium-labeled double cream (200 ml, 24 g fat) was measured in 5 subjects. The rate of gastric emptying of the cream was unaffected by exogenous motilin. Gel chromatographic analysis of basal plasmas revealed two immunoreactive motilin peaks. After ingestion of cream during motilin infusion, there was an increase of the second peak but a reduction of the first peak whereas both peaks rose on the control day. Thus low-dose exogenous motilin stimulates the gastric emptying of glucose but not of fat.