Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit.
Gastroenterology
; 120(2): 361-8, 2001 Feb.
Article
en En
| MEDLINE
| ID: mdl-11159876
ABSTRACT
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 microg. 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Bombesina
/
Vaciamiento Vesicular
/
Receptores de Bombesina
/
Vaciamiento Gástrico
/
Motilidad Gastrointestinal
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Gastroenterology
Año:
2001
Tipo del documento:
Article
País de afiliación:
Suiza