Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit

Background & Aims: This study was designed to characterize [D-F(5)Phe(6)D-A la(11)]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferri ng bombesin receptor antagonist and to determine whether GRP physiologicall y regulates gastrointestinal motility. Intravenous BIM26226 (5-500 mug.kg(- 1).h(-1)) inhibits GRP-induced gallbladder contraction and plasma cholecyst okinin (CCH) 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 emp tying rate (0.11 +/- 0.02%/min vs. 0.26 +/- 0.04%/min [control]), whereas c oncomitant 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 minut es). BIM26226 did not alter plasma CCK response, indicating that circulatin g CCK did not mediate these effects. Conclusions: These data show that BIM2 6226 is a potent antagonist of exogenous and endogenous GRP and suggest tha t GRP is a major physiologic regulator of gastric emptying, smalt bowel tra nsit, and gallbladder contraction.