LEUKOTRIENE-EVOKED CYCLIC CHLORIDE SECRETION IS MEDIATED BY ENTERIC NEURONAL MODULATION IN GUINEA-PIG COLON

Short term exposure to leukotrienes evoked a well known nerve mediated increase in short circuit current. It is unknown whether leukotrienes evoke in addition oscillations in chloride secetion, as has been repo rted for some of the other mediators released during inflammation. The refore, the aim of this study was to characterize the effects of a lon g time exposure of leukotrienes on mucosal functions. Conventional Uss ing chamber and intracellular recording techniques were used to invest igate the actions of leukotriene D-4 and C-4 on short-circuit current and excitability of submucosal neurons in guinea-pig distal colon. In Ussing chambers, long term exposure to leukotriene D-4 or C-4 evoked r hythmic oscillations in short-circuit current in 35% and 50% of tissue s, respectively. These current bursts were blocked by tetrodotoxin, at ropine, hexamethonium and piroxicam. Secretory response to short term exposure of leukotrienes was significantly higher in tissues exhibitin g current bursts. Likewise, the potentiating effects of leukotrienes o n the response to field stimulation was only observed in tissues exhib iting current bursts. In intracellular recording experiments, leukotri ene C-4 evoked activation of submucosal neurons that was partly sensit ive to indomethacin; no oscillations in neuronal excitability could be demonstrated. Results suggested that long term exposure to leukotrien es evoked current bursts that were mediated by neural, cholinergic mec hanisms as well as endogeneous prostaglandins.