Nitric oxide and ATP co-mediate the NANC relaxant response in the guinea-pig taenia caeci

The effect of the nitric oxide synthase inhibitor N-G-nitro-L-arginine (L-NOARG; 100 mu M) and the P-2 purinoceptor antagonist pyridoxalphosphate-6-azopbenyl-2',4'-disulfonic acid (PPADS; 50 mu M) was investigated on the non-adrenergic, non-cholinergic (NANC) relaxant response of the guinea-pig isolated taenia caeci to electrical field stimulation at I or 10 Hz, under isotonic recording conditions. Either drug alone caused an about 50% inhibition, while combining the two drugs nearly abolished the response at both frequencies. The inhibitory effect of L-NOARG (100 mu M) was partly reversed by L-arginine (30 mM). PPADS, but not L-NOARG, inhibited the relaxant effect of exogenous ATP, bur not that of the nitric oxide donor sodium nitroprusside. It is concluded that both nitric oxide and ATP are involved in the mediation of NANC relaxation in the taenia caeci, in an apparently additive manner.