| The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans. | |
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MedLine Citation:
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PMID: 1568584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying. |
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Authors:
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P Cantor; P E Mortensen; J Myhre; I Gjorup; H Worning; E Stahl; T T Survill |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Randomized Controlled Trial |
Journal Detail:
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Title: Gastroenterology Volume: 102 ISSN: 0016-5085 ISO Abbreviation: Gastroenterology Publication Date: 1992 May |
Date Detail:
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Created Date: 1992-05-27 Completed Date: 1992-05-27 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1742-51 Citation Subset: AIM; IM |
Affiliation:
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Department of Clinical Chemistry and Surgical Gastroenterology C, Rigshospitalet, Copenhagen, Denmark. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Benzodiazepinones / pharmacology* Bile Acids and Salts / secretion Cholecystokinin / blood Devazepide Duodenum / metabolism Feedback Food Gallbladder / drug effects*, physiology Gastric Emptying / drug effects Gastrointestinal Motility Humans Hydrogen-Ion Concentration Male Pancreas / drug effects*, secretion Receptors, Cholecystokinin / antagonists & inhibitors* Trypsin / secretion |
| Chemical | |
Reg. No./Substance:
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0/Benzodiazepinones; 0/Bile Acids and Salts; 0/Receptors, Cholecystokinin; 103420-77-5/Devazepide; 9011-97-6/Cholecystokinin; EC 3.4.21.4/Trypsin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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