Role of nitric oxide-dependent and -independent mechanisms in peristalsis and accommodation in the rabbit distal colon

R. Ciccocioppo, L. Onori, E. Messori, S. M. Candura, T. Coccini, M. Tonini

Research output: Contribution to journalArticle

Abstract

Previous findings, which have been confirmed in this study, indicate that nitric oxide (NO)-dependent and -independent (apamin-sensitive) mechanisms underlie the electrically induced non-adrenergic, noncholinergic (NANC) relaxation in the circular muscle of rabbit distal colon. Based on this evidence, we further investigated whether, and to what extent, these separate NANC components participate in the maintenance of circular muscle tone, reflex relaxations evoked by localized balloon distension or during peristalsis (descending inhibition) and in the accommodation of colonic wall in response to graded intraluminal fluid delivery. N(G)-nitro-L-arginine (L- NNA) (10-300 μM), apamin (100 nM) and tetrodotoxin (60 nM), enhanced the spontaneous low tone and phasic activity in circular muscle strips. In experiments on peristalsis, L-NNA (30 and 300 μM) shortened the latency of peristaltic wave initiation and increased the velocity of propulsion of an intraluminally distended balloon (range, 0.1-1 ml). The latter effect was mimicked by the NO scavenger oxyhemoglobin (30 μM). Velocity of propulsion was enhanced by apamin (100 nM) at low balloon distension (0.1 and 0.2 ml), whereas it was reduced at high distension volumes (1 ml), due to disruption of descending inhibition. A combination of L-NNA (300 μM) and apamin (100 nM) blocked peristalsis, due to persisting spasms of the circular muscle. L- NNA (300 μM) did not affect the amplitude of distension-evoked ascending reflex contraction and slightly inhibited the descending reflex relaxation. By contrast, the latter reflex was virtually abolished by apamin (100 nM). L- NNA (300 μM) and tetrodotoxin (0.6 μM), but not apamin (100 nM), reduced colonic wall accommodation (i.e., enhanced the intraluminal pressure) to graded fluid distension. Our findings indicate that neurogenic inhibitions in the rabbit distal colon are mediated by NO-dependent and -independent (apamin-sensitive) mechanisms. They are both involved in the maintenance of spontaneous low tone of the circular muscle, in the reflex relaxations caused by localized gut wall distension and in the descending inhibition during peristalsis, in which the apamin-sensitive component exerts a major role. Conversely, colonic wall accommodation is mediated by a NO pathway. The reported increase in the velocity of propulsion may result from suppression of a tonic inhibitory restraint on the circular muscle and, possibly, on excitatory pathways involved in bolus displacement during peristalsis, leading to unopposed or even enhanced excitatory neurotransmission.

Original languageEnglish
Pages (from-to)929-937
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume270
Issue number3
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Pharmacology

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