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 conscious dogs that had surgically prepared Heidenhain pouchs (HP). Contractile activity was measured by means of chronically implanted force transducers, and changes in pH of the perfusate through the HP were monitored simultaneously. Intravenous infusion of PG (4 micrograms/kg-hr) inhibited motilin-induced phase III activity both in the main stomach and in the HP, whereas histamine (40 micrograms/kg-hr) inhibited activity only in the main stomach. Famotidine (0.3 mg/kg, i.v., the dose that completely inhibited gastric acid secretion by PG or histamine) blocked the inhibition 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 PG-induced decrease in the pH of the perfusate lowered by PG, reversed the inhibition of phase III activity by PG in the HP but not in the main stomach. However, L-364,718, when combined with famotidine, potently reversed the PG-induced inhibition of phase III activity both in the main stomach and in the HP. These results show that the inhibitory effect of PG on motilin-induced phase III activity is brought about by two distinctive mechanisms, gastric acid and the cholecystokinin receptors-dependent mechanism, whereas the histamine-induced inhibition is mediated only by gastric acid. In the vagally denervated HP, however, gastric acid is not involved in an inhibitory effect of PG.