IMPLICATION OF NK1 AND NK2 RECEPTORS IN RAT COLONIC HYPERSECRETION INDUCED BY INTERLEUKIN-1-BETA - ROLE OF NITRIC-OXIDE

Background & Aims: Interleukin (IL) 1 beta is known to induce a neural ly mediated colonic water secretion in vivo. The aim of this study was to investigate the mechanism of action of IL-1 beta on colonic net wa ter flux and the role of tachykinins and nitric oxide. Methods: In ane sthetized rats, isolated colonic loops were infused with Ringer's buff er containing [C-14]polyethylene glycol 4000. Net water flux was calcu lated according to C-14 activity determined in the effluent that was c ollected at 15-minute intervals. Results: Recombinant human IL-1 beta induced a 30-minute colonic hypersecretion. This effect was blocked by NK1 and NK2 antagonists, tetrodotoxin, and N-G-methyl-L-arginine (L-N MA). L-arginine reversed the antisecretory effect of L-NMA on IL-1 bet a-induced hypersecretion but did not modify the IL-1 beta-induced hype rsecretion. Both NK1 and NK2 agonists induced a colonic hypersecretion , and their effects were blocked by L-NMA and tetrodotoxin. The NK3 ag onist had no effect on water movements. The NK2 antagonist abolished t he secretory effect of NK1 agonist; in contrast, the NK1 antagonist ha d no effect on the NK2 agonist-induced secretion. Conclusions: IL-1 be ta-induced colonic hypersecretion in vivo involves NK1- and NK2-recept or activation in cascade, suggesting a release of substance P and neur okinin A acting through NO release.