Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit
| Autor: | Finn Larsen, Silvia Ketterer, Annette Collet, Pius Hildebrand, Livid Rossi, Christoph Beglinger, Fuping Peng, Yolanda Serrano, Lukas Degen |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.medical_specialty Gallbladder Emptying Duodenum Eating chemistry.chemical_compound Gastrin-releasing peptide Internal medicine medicine Humans Single-Blind Method Radionuclide Imaging Cholecystokinin Cross-Over Studies Hepatology Gastric emptying business.industry Gallbladder digestive oral and skin physiology Gastroenterology Bombesin Middle Aged Peptide Fragments Bombesin receptor Receptors Bombesin Endocrinology medicine.anatomical_structure Gastric Emptying Gastrointestinal hormone chemistry Gastrointestinal Motility business hormones hormone substitutes and hormone antagonists |
| Zdroj: | Gastroenterology. 120:361-368 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/gast.2001.21174 |
| Popis: | Background & Aims: This study was designed to characterize [D-F 5 Phe 6 D-Ala 11 ]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5–500 μg · kg −1 · h −1 ) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. Methods: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. Results: Intravenous BIM26226 potently inhibited gastric lag time (114 ± 7 vs. 41 ± 6 minutes [control]) and gastric emptying rate (0.11 ± 0.02%/min vs. 0.26 ± 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 ± 41 vs. 262 ± 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t 50% , 35 ± 4 minutes), which BIM26226 inhibited significantly (t 50% , 64 ± 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. Conclusions: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction. GASTROENTEROLOGY 2001;120:361-368 |
| Databáze: | OpenAIRE |
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