Nitric oxide, an enteric nonadrenergic-noncholinergic relaxant transmitter: evidence using phosphodiesterase V and nitric oxide synthase inhibition.
1. The effects of NG-nitro-L-arginine (L-NOARG), a nitric oxide synthase inhibitor, and SK&F 96231, a phosphodiesterase type V inhibitor, on electrical field stimulated (EFS) nonadrenergic noncholinergic (NANC) relaxations of rat fundal strips, guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, and guinea-pig taenia caeci were investigated. 2. Reproducible repeated control random EFS frequency-response curves were obtained for all three tissues. 3. Depending on the frequency of stimulation, L-NOARG (10(-4)-5 x 10(-3) M) caused either 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 reversed, depending on the tissue, by L-arginine (5 x 10(-3) M). 4. SK&F 96231 (10(-6)-10(-4) M) caused a concentration- and frequency-dependent potentiation of both the size and duration of the EFS-induced NANC relaxant response of rat fundal strips and guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea-pig taenia caeci. 5. Zaprinast, another phosphodiesterase type V inhibitor (10(-6)-10(-4) M) caused a concentration- and frequency-dependent potentiation 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 concentration-dependent relaxation of the agonist-induced tone of all three tissues 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 suggest NO is involved in the NANC nerve-mediated relaxation of rat fundal strips and guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not the guinea-pig taenia caeci.
Biosciences Division, University of Hertfordshire, Hatfield.
S J
SJ
Williams
M E
ME
Parsons
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D019335:Nitroarginine; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects
D004791:Enzyme Inhibitors; D011688:Purinones; C073025:2-(2-propoxyphenyl)-6-purinone; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D010727:Phosphoric Diester Hydrolases