Duodenal acid-induced gastric relaxation is mediated by multiple pathways

In this study, we used an in vivo anesthetized rat model to investigate the mechanisms responsible for duodenal acid-induced inhibition of gastric mot ility. Intraduodenal infusion of HCl produced a rate-dependent decrease in intragastric pressure. Infusion of HCl at 2 ml/h produced a physiological p lasma secretin level and elicited a decrease in intragastric pressure of 3. 0 +/- 0.2 cmH(2)O. Infusion of rabbit secretin antiserum reduced the acid-i nduced inhibition of gastric motility by 85 +/- 5%, suggesting mediation ma inly by endogenous secretin. Administration of the cholecystokinin (CCK)-A antagonist MK-329 caused only a modest 10 +/- 3% reduction in gastric relax ation, whereas the serotonin antagonist ICS-205930 had no effect. In contra st, immunoneutralization with the secretin antibody caused only a 15% reduc tion in the relaxation evoked by a higher rate of HCl infusion (3 ml/h), wh ereas MK-329 and ICS-205930 caused a 20 +/- 4% reduction and no reduction, respectively. Bilateral truncal vagotomy or perivagal application of capsai cin completely abolished gastric relaxation in response to low rates (1-2 m l/h) of 0.1 N HCl infusion but only partially affected gastric relaxation i n response to a higher infusion rate (3 ml/h). These observations indicate that multiple pathways mediate the duodenal acid-induced inhibition of gast ric motility. At low rates of HCl infusion, gastric relaxation is mediated primarily by endogenous secretin, which acts through vagal afferent pathway s. At higher rates of HCl infusion, gastric relaxation is mediated by endog enous secretin, CCK, and possibly by the direct action of HCl on vagal affe rent pathways or yet unidentified neuropathways.