Hyperpolarization and inhibition of contraction mediated by nitric oxide released from enteric inhibitory neurones in guinea-pig taenia coli.

1. Inhibition of nitric oxide synthase by NG-nitro-L-arginine (L-NNA) reduced the neurogenic relaxation of precontracted taenia coli only in the absence of atropine. The membrane hyperpolarization associated with the neurogenic relaxation was also reduced by inhibition of NOS only when atropine was absent. 2. The membrane hyperpolarization associated with the neurogenic relaxation of the taenia coli was inhibited by oxyhaemoglobin only in the absence of atropine. In the presence of atropine, oxyhaemoglobin did not reduce the i.j.p. or nerve evoked relaxation. 3. Inhibition of NOS by L-NNA did not affect the overflow of [3H]-ACh in response to electrical field stimulation (EFS), suggesting that, under the conditions of our experiments, endogenous NO did not modulate release of ACh. Sodium nitroprusside also had no effect on the neurogenic overflow of [3H]-ACh; however, noradrenaline significantly reduced [3H]-ACh overflow. 4. In summary, the postjunctional effects of neurally-released NO are not apparent in guinea-pig taenia coli when atropine is present. This implies muscarinic regulation of NO release or muscarinic regulation of another excitatory substance, such as tachykinin(s), that, when blocked, masks the postjunctional effects of NO. These data, together with previous studies, suggest a possible regulatory role for NO in enteric neurotransmission that may be more prominent in some species or tissues than others.