The effect of gastric inhibitory polypeptide (GIP) on gastric acid secretion in dogs.

Inhibitory effects of gastric inhibitory polypeptide (GIP) on tetragastrin-stimulated gastric acid secretion were studied in five dogs prepared with both Heidenhain fundic pouches and simple gastric fistulae. In the first series of experiments graded doses of GIP, doubling from 0.25 to 2.0 microgram/kg-hr, were given intravenously with a background infusion of 4.0 microgram/kg-hr tetragastrin. In the second experiments graded doses of tetragastrin, doubling from 1.0 to 8.0 microgram/kg-hr, were given intravenously with an additional infusion of 0.5 microgram/kg-hr of GIP. GIP inhibited dose-dependently gastric acid secretion from Heidenhain pouches, but not from simple fistulae. Lineweaver-Burk and Dowd-Riggs transformations of dose-response data obtained with tetragastrin alone and tetragastrin plus GIP showed similar D50 (the dose required for half-maximal response). This indicates that GIP acts as a noncompetitive inhibitor of tetragastrin on acid secretion from the denervated stomach. GIP, however, had no inhibitory effects on acid secretion from the innervated stomach. The cause of this paradoxical effect of GIP remains unknown.