Effect of VIP and PACAP on basal release of serotonin from isolated vascularly and luminally perfused rat duodenum

Publisher Website
Google Scholar
Abstract
The effect of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide-38 (PACAP-38), and PACAP-27 on the release of serotonin (5-HT) into the intestinal lumen and the portal circulation was studied by using in vivo isolated vascularly and luminally perfused rat duodenum. 5-HT levels were determined by HPLC. VIP, PACAP-38, and PACAP-27 reduced the luminal release of 5-HT but did not affect the vascular release of 5-HT. The inhibitory effect caused by VIP, PACAP-38, and PACAP-27 was not affected by either atropine, hexamethonium, TTX, or TTX plus ACh, but it was completely antagonized by the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine (l-NNA). The VIP receptor antagonist VIP-(10—28) blocked the effects of VIP, PACAP-38, and PACAP-27. These results suggest that VIP and PACAP exert a direct inhibitory effect on the luminal release of 5-HT from the enterochromaffin (EC) cells via a common receptor site on the EC cells and that this effect is mediated by NO but not by cholinergic pathways. A single injection of TTX, atropine, or hexamethonium reduced the luminal release of 5-HT, whereas a single injection of VIP-(10—28) stimulated the luminal release of 5-HT and this effect was antagonized by atropine, hexamethonium, or TTX. These results suggest that EC cells may receive the direct innervation of cholinergic neurons as well as VIP and/or PACAP neurons, with the former exerting a tonic stimulatory influence and the latter exerting a tonic inhibitory influence on 5-HT release into the intestinal lumen.