Role of gastrin/CCK-B receptors in meal-stimulated acid secretion in rats.
Gastrin is the principal hormonal mediator of gastric acid secretion. Using an in vivo, intact, anesthetized rat model, we studied the role of gastrin/cholecystokinin (CCK)-B receptors in regulating the release of histamine and somatostatin during intragastric stimulation of acid secretion during a peptone meal. In pylorusligated, adult male rats (each implanted with a gastric cannula and portal venous and splenic artery catheters), after a 30-min basal period, gastric acid secretion was stimulated for 90 min either by an intravenous infusion of gastrin-17 (15 micrograms.kg-1.h-1) or by extragastric titration of 5 ml 8% peptone meal at pH 5.5. Basal and stimulated acid outputs and portal venous plasma gastrin, histamine, and somatostatin concentrations were measured before and after close-arterial injection of a new, relatively selective, gastrin/CCK-B receptor antagonist GR143330X. GR143330X reduced basal acid output by 50% but not basal plasma gastrin, histamine, or somatostatin concentrations. GR143330X reduced gastrin-stimulated acid output by 80%, plasma histamine by 70%, and plasma somatostatin by 34%. During intragastric peptone meal stimulation GR143330X reduced the acid response by 42% during the 30- to 60-min period but not during the 60- to 90-min period. GR143330X reduced the plasma histamine response by 72 and 68%, and the plasma somatostatin response by 32 and 54% during the 30- to 60- and 60- to 90-min periods, respectively. GR143330X did not block the gastrin response to peptone at any time. These results indicate that GR143330X is an effective agent for blocking gastrin-stimulated acid secretion and histamine and somatostatin release in rats. Furthermore, we show for the first time in an intact, in vivo, anesthetized rat model that meal-stimulated activation of gastrin/CCK-B receptors stimulates acid secretion in part by regulating the release of histamine and somatostatin.
Aurang
K
K
Research Service, Department of Veterans Affairs, West Los Angeles Medical Center, California, USA.
Spraggs
C F
CF
Jordan
C
C
Lloyd
K C
KC
D000818:Animals; D004435:Eating / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood / Q000494:pharmacology; D006632:Histamine / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D009994:Osmolar Concentration; D010461:Peptones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D013004:Somatostatin / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology*
C106475:GR143330X; D005755:Gastrins; D010461:Peptones; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013777:Tetrazoles; D013004:Somatostatin; D006632:Histamine