INVOLVEMENT OF INTERLEUKIN-1, PROSTAGLANDINS AND MAST-CELLS IN RECTALDISTENSION-INDUCED COLONIC WATER SECRETION IN RATS

1. In vivo rectal distension (RD) induces a neurally mediated colonic net water hypersecretion in rats. Interleukin-1 beta (IL-1 beta) also induces neural colonic water hypersecretion involving the release of p rostaglandins (PGs) and a mast cell degranulation in rats. This study investigated in vivo the role of IL-1, PGs and mast cells in RD-induce d colonic hypersecretion. 2. Proximal colonic net water flux was deter mined using [C-14]polyethylene glycol (PEG) 4000 (mel. wt, 4000) in an aesthetized rats. On strips taken from the distal colon: (i) a histolo gical analysis was performed to determine the number of mucosal mast c ells (MMC); and (ii) histamine levels were measured by radioimmunoassa y after stimulation with compound 48/80. 3. RD induced a net colonic w ater secretion that was blocked by I.C.V. administration of IL-1ra (an IL-1 receptor antagonist) and indomethacin, and by systemic treatment with doxantrazole and indomethacin. RD decreased the number of reside nt mast cells and the release of histamine from the distal colonic str ips. Moreover, using SDS-PAGE immuno-blotting the expression of IL-1 b eta was detected in the brain. 4. These results suggest that, in rats, RD induces colonic net mater hypersecretion by the activation of a ne uro-immunological reflex pathway, involving brain IL-1 beta, PG releas e and peripheral mast cell degranulation.