Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit.
OBJECTIVE
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.
Degen
L P
LP
Division of Gastroenterology and Department of Research, University Hospital, Basel, Switzerland.
Peng
F
F
Collet
A
A
Rossi
L
L
Ketterer
S
S
Serrano
Y
Y
Larsen
F
F
Beglinger
C
C
Hildebrand
P
P
D000328:Adult; D001839:Bombesin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D002766:Cholecystokinin / Q000097:blood; D018592:Cross-Over Studies; D004386:Duodenum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D004435:Eating / Q000502:physiology; D016473:Gallbladder Emptying / Q000187:drug effects* / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D011877:Radionuclide Imaging; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D016037:Single-Blind Method
C091872:BIM 26226; D010446:Peptide Fragments; D018004:Receptors, Bombesin; D002766:Cholecystokinin; D001839:Bombesin