Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon.

Previous evidence suggests that nonadrenergic, noncholinergic (NANC) inhibitory neurotransmission in visceral muscles may be mediated by nitric oxide (NO). We have demonstrated that NO and the NO carrier S-nitrosocysteine can mimic the hyperpolarization in colonic muscle caused by nerve stimulation. The finding that S-nitrosocysteine breaks down fast enough to cause inhibitory junction potential (IJP)-like hyperpolarizations suggests that NO could be stored as a nitrosothiol in secretory vesicles in nerve terminals. Oxyhemoglobin blocked hyperpolarization responses to NO and S-nitrosocysteine and NANC IJPs. These findings suggest that NO is a biologically active transmitter substance in NANC inhibitory neurotransmission. NO enhanced the open probability of Ca(2+)-activated K+ channels in isolated colonic muscle cells. These channels may mediate the hyperpolarization response to NANC neurotransmission in colonic muscles.