Inhibition of anaphylaxis-evoked intestinal fluid secretion by the dual application of an H1 antagonist and cyclooxygenase inhibitor.
The regulation of anaphylaxis-mediated fluid secretion by the small intestine was examined in rats immunized by infection with Trichinella spiralis and reinfected by intraduodenal injection with L1 larvae. Net fluid secretion, which was measured as the volume of fluid present in the intestine 30 minutes after the challenge infection, was significantly greater in both actively and passively immunized rats than in nonimmune rats. The amount of fluid recovered from the immune host was equivalent to that secreted in response to 50 micrograms/kg of prostaglandin E2 or 250 micrograms/kg of cholera toxin. Worm-induced fluid secretion in immune hosts was reduced by treatment with diphenhydramine and inhibited by the dual application of diphenhydramine and indomethacin. Indomethacin alone had no effect despite inhibiting mucosal prostaglandin synthesis. Fluid secretion was unaltered by prior treatment of immune rats with a 5-lipoxygenase inhibitor, L-651,392, and only slightly reduced when L-651,392 was used in combination with indomethacin. After a challenge infection, more histamine was released into intestinal loops of immune rats than those of nonimmune rats. Prechallenge treatment of immune rats with indomethacin caused a twofold increase in histamine release. In summary, anaphylaxis-induced fluid secretion in the small intestine is mediated largely by histamine and cyclooxygenase products. This secretion can be lowered by treatment with diphenhydramine and further reduced by diphenhydramine in combination with indomethacin. The paradoxical effects of indomethacin when used alone and in combination with diphenhydramine are explained by the downregulation of histamine release by products of the cyclooxygenase pathway.
Zhang
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S
Department of Physiology and Cell Biology, University of Texas Medical School, Houston.
Myers
S
S
Castro
G A
GA
D000704:Analysis of Variance; D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002712:Chlorides / Q000378:metabolism; D004155:Diphenhydramine / Q000494:pharmacology; D004357:Drug Synergism; D006634:Histamine H1 Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D006636:Histamine Release / Q000502:physiology; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology; D007419:Intestinal Secretions / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D010640:Phenothiazines / Q000008:administration & dosage* / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014234:Trichinella / Q000276:immunology; D014235:Trichinellosis / Q000276:immunology
D000947:Antigens, Helminth; D002712:Chlorides; D006634:Histamine H1 Antagonists; D016859:Lipoxygenase Inhibitors; D010640:Phenothiazines; D011453:Prostaglandins; D004155:Diphenhydramine; C053726:4-bromo-2,7-dimethoxy-3H-phenothiazin-3-one; D007213:Indomethacin