Nonadrenergic noncholinergic neurotransmitter of feline trachealis: VIP or nitric oxide?

We tested the hypothesis that vasoactive intestinal peptide (VIP) or nitric oxide (NO) is the nonadrenergic noncholinergic (NANC) neurotransmitter in feline trachealis. Isometric tension was measured in trachealis (open or closed tracheal rings) in vitro. Propranolol (10 microM) and atropine (1 microM) were present throughout the experiment, and smooth muscle tone was increased to 60-90% maximal with 5-hydroxytryptamine. We used three methodologies to reduce the relaxation function of VIP, which in turn should reduce NANC-mediated relaxation. 1) The putative VIP antagonist peptide T (10 microM) did not affect VIP concentration-response curves or electrical field stimulation- (EFS) induced NANC responses. 2) Incubation of tissue in specific VIP antiserum (16 h at 4 degrees C) did not reduce EFS-induced NANC relaxations relative to tissue incubated in normal rabbit serum (P > 0.05). On the basis of our passive immunization techniques, it is not possible to absolutely reject VIP as the NANC transmitter. We speculate that nonspecific peptidases present in normal serum and VIP antiserum reduce EFS-induced responses similarly. 3) VIP desensitization, confirmed by a significant rightward shift (P < 0.01) in the VIP concentration-response curve, was achieved by exposing tissues (n = 11) to 1.0 microM VIP for 30 min. Desensitization did not reduce the EFS-induced NANC relaxatory response (P < 0.05) compared with control tissues, suggesting that VIP is not the NANC mediator.(ABSTRACT TRUNCATED AT 250 WORDS)