PACAP and VIP inhibit pyloric muscle through VIP/PACAP-preferring receptors

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with structural homology to vasoactive intestinal polypeptide (VIP). Two receptor types for PACAP have been described: PACAP preferring receptors are selective for PACAP; whereas VIP/PACAP preferring receptors have similar affinity for both PACAP and VIP. Both VIP and PACAP are present in enteric nerves at the pylorus. VIP is known to exert inhibitory effects on pyloric muscle; the effect of PACAP is unknown. The aims of this study were to determine the effect of PACAP on pyloric muscle and to characterize the PACAP receptor. METHODS: Rabbit pyloric muscle strips were cut parallel to circular muscle fibres and placed in muscle baths. The effect of PACAP and VIP were quantitated as percent of basal motility index (MI). RESULTS: PACAP-27, PACAP-38, and VIP had dose dependent inhibitory effects on the spontaneous phasic contractions of the pylorus. The PACAP-27- induced relaxation was inhibited by the PACAP receptor antagonist PACAP6-27, but was not affected by tetrodotoxin. VIP also had dose dependent inhibitory effects on pyloric muscle. The VIP relaxation was inhibited by PACAP6-27, but not affected by tetrodotoxin. CONCLUSIONS: These studies indicate that, similar to VIP, PACAP inhibits pyloric muscle. The inhibitory effect of the PACAP receptor antagonist on both PACAP and VIP-induced relaxation suggest that PACAP and VIP act at the same receptor, a VIP/PACAP preferring receptor.