DIFFERENTIAL-EFFECTS OF INFLAMMATORY MEDIATORS ON ION SECRETION IN THE GUINEA-PIG COLON

Bi-directional interactions between the enteric nervous system and the immune system play an important role in,out inflammation. We therefor e investigated the effects of the inflammatory mediators, prostaglandi n (PGD(2), PGE(2), PGI(2), and PGF(2 alpha)) and leukotriene (LTC4), o n guinea-pig colonic secretion and on electrophysiological behaviour o f submucosal neurones. In Ussing chambers, all inflammatory mediators evoked a dose-dependent increase in short circuit current (I-sc) that represented electrogenic chloride secretion. The secretory response wa s significantly reduced by tetrodotoxin (TTX) and atropine suggesting involvement of cholinergic submucosal neurones. Long-term application of prostaglandins and LTC4 induced TTX- and atropine-sensitive cyclica l chloride secretions. Intracellular recordings revealed activation of submucosal neurones by all inflammatory mediators. This activation co nsisted of depolarisation of the membrane associated with increased sp ike discharge. Frequently, prostaglandins and LTC4 induced spontaneous occurrence of cholinergic fast excitatory postsynaptic potentials. Re sults suggest that the role of the enteric nervous system in neuroimmu ne interactions consists of a potentiation of the direct epithelial ef fect of inflammatory mediators by the activation of submucosal neurone s. Ongoing nerve-mediated cyclical changes in chloride secretion may b e interpreted as the induction of intrinsic alarm programs. The effect s of inflammatory mediators may serve as a defense mechanism to dilute noxious substances in the lumen. (C) 1997 Elsevier Science Inc.