Inhibition of immune complex-induced enteropathy by three different platelet-activating factor receptor antagonists

Prostaglandins
K J BlochM B Bloch

Abstract

We previously showed that intravenous injection of rat anti-BSA-BSA complexes (IC) prepared in 5x antigen excess rapidly induced a striate pattern of serosal (to mucosal) hemorrhage and vascular congestion throughout the small intestine of the Sprague-Dawley rat. In this study, we tested the effect of three different platelet-activating factor (PAF) receptor antagonists on the development of lesions. L-652,731, a synthetic derivative of kadsurenone (at doses of 1.3-2.7 mg/kg), SRI 63-675, a substituted quinolinium compound (6.7-15 mg/kg), and WEB 2086, a thienotriazolodiazepine (5-25 mg/kg) were each capable of completely or partially inhibiting IC-induced enteropathy in the majority of animals tested. Pretreatment with WEB 2086 prevented IC-induced hemoconcentration but not neutropenia. The antagonists did not lower the level of blood complement nor interfere with the fall in complement induced by administration of IC. The ability of PAF receptor antagonists to completely or partially inhibit IC-induced small intestinal lesions suggests that endogenous PAF is a major mediator of IC-induced enteropathy.

References

Feb 1, 1989·The Journal of Clinical Investigation·J S WarrenP A Ward
Jul 1, 1986·Digestive Diseases and Sciences·S E KirkhamW A Walker
Sep 23, 1987·European Journal of Pharmacology·D A HandleyR N Saunders
Nov 1, 1988·Gastroenterology·W F Stenson
Jul 1, 1986·Prostaglandins·J L Wallace, B J Whittle
Oct 1, 1964·Proceedings of the Society for Experimental Biology and Medicine·W A HOOK, L H MUSCHEL

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Citations

Nov 1, 1996·The Journal of Pharmacy and Pharmacology·A A Izzo
Mar 1, 1994·Prostaglandins, Leukotrienes, and Essential Fatty Acids·S P Travis, D P Jewell

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