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 gut inflammation. We therefore investigated the effects of the inflammatory mediators, prostaglandin (PGD2, PGE2, PGI2, and PGF2 alpha) and leukotriene (LTC4), on guinea-pig colonic secretion and on electrophysiological behaviour of submucosal neurones. In Ussing chambers, all inflammatory mediators evoked a dose-dependent increase in short circuit current (Isc) that represented electrogenic chloride secretion. The secretory response was 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 cyclical chloride secretions. Intracellular recordings revealed activation of submucosal neurones by all inflammatory mediators. This activation consisted of depolarisation of the membrane associated with increased spike discharge. Frequently, prostaglandins and LTC4 induced spontaneous occurrence of cholinergic fast excitatory postsynaptic potentials. Results suggest that the role of the enteric nervous system in neuroimmune interactions consists of a potentiation of the direct epithelial effect of inflammatory mediators by the activation of submucosal neurones. Ongoing nerve-mediated cyclical changes in chloride secretion may be interpreted as the induction of intrinsic alarm programs. The effects of inflammatory mediators may serve as a defense mechanism to dilute noxious substances in the lumen.
Frieling
T
T
Department of Gastroenterology, University of Düsseldorf, Germany.
Rupprecht
C
C
Dobreva
G
G
Schemann
M
M
D000818:Animals; D003106:Colon / Q000294:innervation / Q000378:metabolism*; D004558:Electric Stimulation; D006168:Guinea Pigs / Q000502:physiology*; D018836:Inflammation Mediators / Q000502:physiology*; D007477:Ions; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology; D013368:Submucous Plexus / Q000166:cytology / Q000502:physiology
D018836:Inflammation Mediators; D007477:Ions