Pituitary adenylate cyclase activating peptide induces cGMP-mediated relaxation in guinea-pig airways

The mechanism of relaxation of the guinea-pig trachea induced by pituitary adenylate cyclase activating peptide (PACAP)-27 was investigated. We examined whether modulators of nitric oxide (NO) and carbon monoxide (CO) affect PACAP-induced response of tracheal strips in vitro. Pretreatment with N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) and L-arginine (L-arg) had no effect, while 1H-\1,2,4\ oxadiazolo\4,3-a\quinoxalin-1-one (ODQ), haemoglobin and zinc protoporphyrin IX (Zn PP-9) partially abolished the PACAP-induced relaxation, PACAP-27 elevated cyclic GMP level in airway smooth muscle tissue, These results indicate that PACAP-27 not only induces cyclic AMP-mediated responses, but also cyclic GRIP-mediated responses in the airway. In addition, CO is related to the PACAP-induced elevation of cGMP level in the tracheal tissue. (C) 1998 Academic Press.