Involvement of interleukin-1, prostaglandins and mast cells in rectal distension-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 prostaglandins (PGs) and a mast cell degranulation in rats. This study investigated in vivo the role of IL-1, PGs and mast cells in RD-induced colonic hypersecretion. 2. Proximal colonic net water flux was determined using [C-14]polyethylene glycol (PEG) 4000 (mel. wt, 4000) in anaesthetized rats. On strips taken from the distal colon: (i) a histological analysis was performed to determine the number of mucosal mast cells (MMC); and (ii) histamine levels were measured by radioimmunoassay after stimulation with compound 48/80. 3. RD induced a net colonic water 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 resident mast cells and the release of histamine from the distal colonic strips. Moreover, using SDS-PAGE immuno-blotting the expression of IL-1 beta was detected in the brain. 4. These results suggest that, in rats, RD induces colonic net mater hypersecretion by the activation of a neuro-immunological reflex pathway, involving brain IL-1 beta, PG release and peripheral mast cell degranulation.