Sustained relaxant action of [Arg(15,20,21), Leu(17)]-PACAP-27-NH2 on carbachol-induced contraction of guinea-pig tracheal smooth muscle in vitro

摘要

Duration of relaxant action of an analogue of pituitary adenylate cyclase activating peptide (PACAP)-27, rArg(15,20,21), Leu(17)]-PACAP-27-NH2, was compared with that of PACAP-27 in the smooth muscle isolated fi om guinea-pig trachea, The relaxant action was examined on the prolonged contracted state of the smooth muscle, which had been stimulated with carbachol (CCh; 0.1 mu M). Addition of the analogue caused concentration-dependent relaxation; both the onset and offset of which were much slower than those with PACAP-27, vasoactive intestinal polypeptide (VIP), and peptide histidine isoleucine (PHI), More than 90% of the maximum relaxation was maintained for 6 h after addition of the analogue, whereas the relaxation induced by PACAP-27, VIP, and PI-II reached a maximum by 20 min after the addition and was followed by gradual contraction, Influence of peptidases involved in the smooth muscle preparation on the peptides was examined using 10 mu M captopril and 1 mu M phosphoramidon as peptidase inhibitors. Although the efficacy and duration of the relaxant action with PACAP-27 were significantly potentiated in the presence of peptidase inhibitors, those with the analogue were only slightly affected, A conclusion is drawn that the analogue has sustained relaxant action on CCh-induced contraction of the tracheal smooth muscle, and that this sustained action is, at least in part, due to much lower ii susceptibility of the analogue to degradation by peptidases, implying an advantage of the analogue in clinical application. [References: 18]