Pituitary adenylate cyclase-activating polypeptide (PACAP) induces duodenal phasic contractions via the vagal cholinergic nerves in sheep.

This study examined the effect of intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP) on duodenal motility in sheep and the mechanism of the action of PACAP. The bilateral cervical vagus nerves were coiled with a cooling device under anesthesia. Duodenal motility was recorded by manometry in conscious animals. PACAP-27, PACAP-38 and vasoactive intestinal polypeptide (VIP) were infused intravenously at 3, 10, 30 and 100 pmol/kg in phase II of the duodenal migrating motor complexes (MMC). PACAP-27 induced a cluster of phasic contractions of the duodenum, while PACAP-38 only augmented the spontaneous contractions. The pattern of PACAP-27-induced contractions was different from that of phase III of MMC, and the contractions were followed by a quiescence period. VIP at only the highest dose induced phase III-like activity of the duodenum. Both the intravenous background infusion of atropine at 10 nmol/kg/min and the reversible cooling blockade of the bilateral cervical vagus nerves blocked the effect of PACAP-27. The application of PACAP-27 at concentrations ranging from 10 nM to 1 microM did not induce contractions of ovine duodenal smooth muscles. These results indicate that PACAP contracts the ovine duodenum via the vagal cholinergic efferent fibers, suggesting that PACAP acts on the central nervous system.