5-HT3 and histamine H± receptors mediate afferent nerve sensitivity to intestinal anaphylaxis in rats

Abstract

Background & Aims: The mechanisms underlying brain stem activation during antigen challenge have not been resolved. Our aim was to characterize afferent nerve responses to intestinal anaphylaxis and determine the mediators involved in afferent activation. Methods: Mesenteric afferent discharge was recorded electrophysiologically after intestinal anaphylaxis in anesthetized rats previously sensitized to chicken egg albumin (EA). Results: Mesenteric afferent nerve discharge increased approximately 1 minute after luminal antigen but not bovine serum albumin (P < 0.001, EA vs. bovine serum albumin). Subsequent administration of antigen had no effect, but systemic EiA evoked a marked increase in afferent discharge (P < 0.05). Afferent responses were unrelated to intestinal motor activity, and the response to luminal antigen was attenuated by luminal anesthetic (1% lidocaine). The 5-HT3-receptor antagonist alosetron (30 n-g kg"1) and the histamine Hi-receptor antagonist pyrilamine (5 mg kg"1) markedly attenuated the response to luminal antigen; pretreatment with doxantrazole attenuated responses to both luminal and systemic antigen. Conclusions: 5-HT3 and histamine, released from mast cells after intestinal anaphylaxis, stimulate mesenteric afférents via 5-HT3 and histamine H! receptors. Information on intestinal immune status is rapidly relayed to the centra nervous system and may play a role in neural reflexes and behavioral responses following activation of the immune system. © 2000 by the American Gastroenterological Association.