INVOLVEMENT OF PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE IN OPOSSUM INTERNAL ANAL-SPHINCTER RELAXATION

Despite its widespread distribution and significance in the gut, the r ole of pituitary adenylate cyclase-activating peptide (PACAP) in inter nal anal sphincter (LAS) relaxation has not been examined. This study examined the role of PACAP in nonadrenergic noncholinergic (NANC) nerv e-mediated relaxation of IAS smooth muscle. Circular smooth muscle str ips from the opossum IAS were prepared for measurement of isometric te nsion. The influence of PACAP and vasoactive intestinal peptide (VIP) antagonists and tachyphylaxis on the neurally mediated IAS relaxation was examined either separately or in combination. The release of these neuropeptides in response to NANC nerve stimulation before and after the nitric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine and NO was also investigated. Both PACAP and VIP antagonists caused signif icant attenuation of LAS relaxation by NANC nerve stimulation. The com bination of the antagonists, however, did not have an additive effect on IAS relaxation. VIP tachyphylaxis caused significant suppression of IAS relaxation by NANC nerve stimulation. PACAP and VIP were found to be released by NANC nerve stimulation and exogenous NO. The data sugg est the involvement of PACAP in IAS relaxation primarily by the activa tion of PACAP(1)/VIP receptor and lack of its independent role in the relaxation. Furthermore, NO may regulate the presynaptic release of PA CAP and VIP.