Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist.
OBJECTIVE
The main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to determine if endogenous GRP is a physiological regulator of gastric acid secretion and gastrin release.


METHODS
Our study consisted of three parts. In part I, subjects received saline or BIM26226 followed by graded doses of intravenous human GRP in a four period crossover design. In part II, subjects received BIM26226 or saline during oral meal ingestion or modified sham feeding. In part III, subjects received an acidified meal in the presence and absence of BIM26226 in a two period crossover design. In addition, gastrin and somatostatin mRNA were measured in biopsy specimens during saline and BIM26226 infusion.


RESULTS
BIM26226 dose dependently inhibited GRP induced acid output. Acid secretion after oral liquid meal intake and sham feeding was significantly inhibited by BIM26226 (p<0.01) whereas plasma gastrin release remained unchanged. Gastrin and somatostatin mRNAs were not significantly different after saline or BIM26226.


CONCLUSIONS
BIM26226 is a potent GRP antagonist in humans. Endogenous GRP may be a physiological regulator of gastric acid secretion. Gastrin release does not seem to be under the control of GRP.
Hildebrand
P
P
Division of Gastroenterology and Department of Research, University Hospital, CH-4031 Basel, Switzerland.
Lehmann
F S
FS
Ketterer
S
S
Christ
A D
AD
Stingelin
T
T
Beltinger
J
J
Gibbons
A H
AH
Coy
D H
DH
Calam
J
J
Larsen
F
F
Beglinger
C
C
D000328:Adult; D000704:Analysis of Variance; D015152:Blotting, Northern; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004435:Eating / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D019886:Gastrin-Releasing Peptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D005755:Gastrins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013004:Somatostatin / Q000032:analysis; D018709:Statistics, Nonparametric
C091872:BIM 26226; D005755:Gastrins; D010446:Peptide Fragments; D012333:RNA, Messenger; D013004:Somatostatin; D019886:Gastrin-Releasing Peptide; D001839:Bombesin