Pituitary adenylate cyclase activating peptide mediates inhibitory nonadrenergic noncholinergic relaxation

We investigated the contribution of pituitary adenylate cyclase activating peptide (PACAP) to inhibitory nonadrenergic noncholinergic (inhibitory-NANC ) relaxation of tracheal smooth muscle in cats. We also investigated the ro les of vasoactive intestinal peptide (VIP) and nitric oxide (NO) on this fu nction. Smooth muscle strips prepared from feline trachea were precontracte d with 1 mu M serotonin, and inhibitory-NANC relaxation was induced by elec trical-field stimulation in the presence of atropine and propranolol. PACAP -(6-38) (a selective antagonist of PACAP; 1, 3 and 10 mu M), VIP-(10-28) (a selective antagonist of VIP; 1, 3 and 10 mu M) and N-omega-nitro-L-arginin e methyl ester (L-NAME, a selective NO synthase inhibitor; 3, 10 and 30 mu M) each partially but significantly attenuated the amplitude of inhibitory- NANC relaxation. The effects of PACAP-(6-38) and VIP-(10-28) were additive. Addition of PACAP-(6-38) and/or VIP-(10-28) further attenuated relaxation in the presence of L-NAME. These results suggest that PACAP, VIP and NO con tribute to the relaxation induced by inhibitory-NANC in tracheal smooth mus cle in cats, and that they mediate this relaxation via different pathways. (C) 2000 Elsevier Science B.V. All rights reserved.