Neural control of the release and action of secretin.

The release and physiological actions of secretin on pancreatic exocrine secretion and gastric secretion of acid and motility are regulated by neuro-hormonal control. The release of secretin by duodenal acidification is mediated by a secretin releasing peptide (SRP). The release and action of SRP are neurally mediated depending on vagal afferent pathway. SRP activity in acid perfusate of the duodenum was substantially decreased when rats were treated with tetradotoxin (TTX), perivagal application of capsaicin, a beta-adrenergic blocker, Met-enkephalin (MEK) or vagotomy. The release of secretin by SRP was abolished in rats treated with TTX, mucosal or perivagal application of capsaicin, MEK or vagotomy. Both release of secretin and pancreatic exocrine secretion (PES) elicited by duodenal acidification were also inhibited dose-dependently by Met-enkepahlin, 5-HT(2) antagonist, ketanserin and 5-HT(3) antagonist, ondansetron. Stimulation of PES and inhibition of gastric acid secretion and motility by secretin in a physiological dose are also dependent on the vagal afferent pathway as these effects of secretin are abolished by perivagal capsaicin treatment or vagotomy. In conscious rats, vagotomy, vagal ligation, or perivagal colchicine but not capsaicin treatment reduced the number of secretin binding sites in the forestomach suggesting another mode of neural regulation that affects gastric motility. Except in the rat, stimulation of PES by secretin in a physiological dose is profoundly inhibited by atropine indicating the importance of a cholinergic input. In isolated and perfused rat pancreas, electrical field stimulation potentiated secretin-stimulated PES that was suppressed by atropine and anti-GRP serum, suggesting the roles of intrapancreatic cholinergic and GRP-containing neurons. In rats, secretin-stimulated PES was inhibited by a NO synthase inhibitor suggesting mediation by NO. However, the neuropeptides and neurotransmitters involved in regulation of the release and action of secretin and their sites of action remain to be elucidated.