INHIBITION OF MOTILIN-INDUCED PHASE-III CONTRACTIONS BY PENTAGASTRIN IN HEIDENHAIN POUCH DOGS

We compared the inhibitory effects of histamine and pentagastrin (PG) on motilin-induced upper gastrointestinal phase III activity in consci ous dogs that had surgically prepared Heidenhain pouchs (HP). Contract ile activity was measured by means of chronically implanted force tran sducers, and changes in pH of the perfusate through the HP were monito red simultaneously. Intravenous infusion of PG (4 mu g/kg-hr) inhibite d motilin-induced phase III activity both in the main stomach and in t he HP, whereas histamine (40 mu g/kg-hr) inhibited activity only in th e main stomach. Famotidine (0.3 mg/kg, i.v., the dose that completely inhibited gastric acid secretion by PG or histamine) blocked the inhib ition of phase III activity induced by histamine but did not affect PG -induced inhibition. L-364,718 (1 mg/kg, i.v.), which had no effect on the PC-induced decrease in the pH of the perfusate lowered by PG, rev ersed the inhibition of phase III activity by PG in the HP but not in the main stomach. However, 1-364,7-18, when combined with famotidine, potently reversed the PC-induced inhibition of phase III activity both in the main stomach and in the HP. These results show that the inhibi tory effect of PG on motilin-induced phase III activity is brought abo ut by two distinctive mechanisms, gastric acid acid the cholecystokini n receptors-dependent mechanism, whereas the histamine-induced inhibit ion is mediated only by gastric acid. In the vagally denervated HP, ho wever, gastric acid is not involved in an inhibitory effect of PG.