NITRIC-OXIDE, AN ENTERIC NONADRENERGIC-NONCHOLINERGIC RELAXANT TRANSMITTER - EVIDENCE USING PHOSPHODIESTERASE-V AND NITRIC-OXIDE SYNTHASE INHIBITION

1 The effects of N-G-nitro-L-arginine (L-NOARG), a nitric oxide syntha se inhibitor, and SK&F 96231, a phosphodiesterase type V inhibitor, on electrical held stimulated (EFS) nonadrenergic noncholinergic (NANC) relaxations of rat fundal strips, guinea-pig isolated ileum longitudin al muscle with intact myenteric plexus, and guinea-pig taenia caeci we re investigated. 2 Reproducible repeated control random EFS frequency- response curves were obtained for all three tissues. 3 Depending on th e frequency of stimulation, L-NOARG (10(-4) -5 x 10(-3) M) caused eith er a complete or partial inhibition of the NANC-induced relaxations of the rat fundal strips and the guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea-pig taenia caeci. The inhibitory action of L-NOARG was partially or totally rever sed, depending on the tissue, by L-arginine (5 x 10(-3) M). 4 SK&F 962 31 (10(-6) -10(-4) M) caused a concentration- and frequency-dependent potentiation of both the size and duration of the EFS-induced NANC rel axant response of rat fundal strips and guinea-pig isolated ileum long itudinal muscle with intact myenteric plexus, but not of the guinea-pi g taenia caeci. 5 Zaprinast, another phosphodiesterase type V inhibito r (10(-6) -10(-4) M) caused a concentration- and frequency-dependent p otentiation of the NANC relaxant responses to EFS of rat fundal strips . 6 SK&F 96231 and zaprinast alone (10(-6) -10(-4) M) caused a concent ration-dependent relaxation of the agonist-induced tone of all three t issues with the maximum degree of relaxation found to be in the order stomach < ileum < caecum. This is the reverse order for ability of SK& F 96231 to potentiate relaxant responses to EFS. 7 These results sugge st NO is involved in the NANC nerve-mediated relaxation of rat fundal strips and guinea-pig isolated ileum longitudinal muscle with intact m yenteric plexus, but not the guinea-pig taenia caeci.