Functional antagonism between nitric oxide and ATP in the motor responses of guinea-pig ileum

1 The interaction of nitric oxide and ATP in the non-adrenergic, non-cholinergic (NANC) motor responses and the presence of NADPH-diaphorase and quinacrine-positive myenteric neurones were studied on guinea-pig ileum using mechanographic, histochemical and quinacrine-fluorescence techniques. In the presence of phentolamine, propranolol and atropine, the non-precontracted longitudinally oriented organ bath preparations responded to sodium nitroprusside (1-100 muM) or ATP (5-50 muM) with tetrodotoxin (0.1 muM)-resistant relaxation or contraction, respectively. The effects of ATP were suramin (50 muM)- and apamin (5 muM)-sensitive. 2 The NANC motor responses elicited by electrical stimulation (0.8 ms, 1-20 Hz, 20 s) consisted of tetrodotoxin-sensitive relaxation phase followed by a phase of twitch-like and tonic contractions. 3 N-G-nitro-L-arginine (L-NNA, 0.1-0.5 mM) inhibited or abolished the relaxation phase. L-arginine (0.5 mM), but not D-arginine (0.5 mM), restored the relaxation phase in L-NNX-pretreated preparations. The relaxation phase increased after ATP-induced desensitization of purinoceptors and in the presence of suramin (50 muM) bur was abolished by apamin (5 muM). 4 The phase of contractions was enhanced by L-NNA (0.1-0.5 mM) and restored by L-arginine (0.5 mM). The twitch-like and tonic contractions were decreased during ATP-induced purinoceptor desensitization and in the presence of suramin (50 muM). Apamin (5 muM) inhibited the tonic contractions. 5 The desensitization of purinoceptors by ATP did not change the L-NNA-induced inhibition of the relaxation phase but decreased the L-NNA-increased phase of contractions. L-NNA reduced the relaxation phase and increased the phase of contractions during purinoceptor desensitization 6 We conclude that in the longitudinal muscle layer of the guinea-pig ileum, nitric oxide mediates the relaxation phase while ATP contributes via smooth muscle P-2 purinoceptors to the phase of contractions suggesting a postjunctional functional antagonism between nitric oxide and ATP. The presence of NADPH-diaphorase- and quinacrine-positive neuronal cells and processes running to the muscle cells confirms a physiological role of nitric oxide and ATP in the ileal neurotransmission.