Effects of spiroglumide, a gastrin receptor antagonist, on acid secretion in humans.
BACKGROUND
A gastrin receptor antagonist, CR2194 (spiroglumide), was used to explore the physiological role of gastrin in regulating gastric acid secretion in humans.


METHODS
The effect of CR2194 on inhibition of gastrin-stimulated acid output was evaluated in a four-period crossover study. Each subject received intravenous doses of 1, 2.5 or 7.5 mg kg-1 h-1 CR2194 or saline (control) followed by graded increasing doses of gastrin (6.4-800 pmol kg-1 h-1). Secondly, the effect of CR2194 on meal-stimulated intragastric acidity was evaluated by infusing either saline (control) or CR2194 (7.5 mg kg-1 h-1) before and after food ingestion.


RESULTS
Acid secretion was dose-dependently inhibited by CR2194. With CR2194, acidity was significantly reduced in the pre-meal and post-prandial period (P < 0.01 and 0.002 respectively), and the integrated gastrin response was augmented to 8.0 +/- 1.4 ng mL-1 240 min compared with 1.5 +/- 0.8 ng mL-1 240 min in the control experiment (P < 0.01). Finally, acid secretion in response to sham feeding was significantly reduced: 15.9 +/- 0.9 mmol 90 min-1 in the control experiment compared with 2.8 +/- 0.9 mmol 90 min-1 during CR2194 infusion (P < 0.05).


CONCLUSIONS
Gastrin receptor blockade with CR2194 alters gastric acid secretion in response to food ingestion or to sham feeding. The results support a physiological role for gastrin in regulating acid secretion in humans.
Beltinger
J
J
University Hospital, Basle, Switzerland. beglinger@tmr.ch
Hildebrand
P
P
Drewe
J
J
Christ
A
A
Hlobil
K
K
Ritz
M
M
D'Amato
M
M
Rovati
L
L
Beglinger
C
C
D000328:Adult; D005502:Food; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007651:Keto Acids / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013141:Spiro Compounds / Q000494:pharmacology*; D013997:Time Factors
D005755:Gastrins; D007651:Keto Acids; D011949:Receptors, Cholecystokinin; D013141:Spiro Compounds; C076954:spiroglumide