Evidence that nitric oxide mediates non-adrenergic non-cholinergic relaxation induced by GABA and electrical stimulation in the rat isolated duodenum

1 GABA (3 x 10(-4) hi) and electrical stimulation (60 mV, 1 ms, 0.1 Hz) produced a non-adrenergic non-cholinergic (NANC) relaxation response in the rat isolated duodenum. 2 Tetrodotoxin (10(-6) M) incubation abolished GABA and electrical stimulation responses but not ATP (10(-3) M)-induced relaxation. 3 Desensitization to ATP (10(-3) M) or alpha,beta-methylene ATP (10(-5) M) and incubation with the P-1 receptor antagonist 8-phenyltheophylline (10(-5) M) failed to affect relaxation induced by GABA and low frequency electrical stimulation. 4 The inhibitor of L-arginine-NO synthase N-omega-Nitro-L-arginine methyl ester (L-NAME) (10(-4)-3 x 10(-4) M) reduced the NANC relaxations elicited by GABA and low frequency electrical stimulation in a dose-dependent manner. These effects were partially reversed by the addition of L-arginine (10(-3)-3 x 10(-3) M). ATP (10(-3) M)-induced relaxations were not modified by L-NAME (3 x 10(-4) M) incubation. 5 These results suggest that nitric oxide is involved in inhibitory NANC transmission in the rat duodenum. We provided original evidence that nitric oxide is involved in neurally mediated relaxations induced by GABA in rat isolated duodenum.