Involvement of nitric oxide in the inhibitory innervation of the human isolated colon.

Abstract

The exact nature of the inhibitory nonadrenergic noncholinergic (NANC) neurotransmitter in the human colon is still unknown. The present study was designed to investigate the role of nitric oxide (NO) and adenosine 5'-triphosphate (ATP) in circular muscle strips of the human isolated colon. NO and ATP induced tetrodoloxin-resistant relaxations that mimicked those evoked by nerve stimulation. Apamin inhibited the response to ATP, had a variable effect on the relaxations to transmural stimulation, and had no effect on those to NO or nitroglycerin. NG-nitro-L-arginine (L-NNA) concentration dependently reduced the NANC nerve-mediated relaxations, but had no effect on those to ATP, NO, or nitroglycerin; the L-NNA resistant part of the NANC relaxation to nerve stimulation was further reduced by apamin. The inhibitory effect of L-NNA or the combination of L-NNA and apamin was prevented by L-arginine but not by D-arginine. These results suggest that NO and another substance, perhaps ATP, are involved in the inhibitory NANC neurotransmission in the circular muscle of the human colon.