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

Abstract

BACKGROUND: The exact nature of the inhibitory nonadrenergic noncholinergic (NANC) neurotransmitter in the human colon is still unknown. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggest that NO and another substance, perhaps ATP, are involved in the inhibitory NANC neurotransmission in the circular muscle of the human colo