EVIDENCE FOR A COLONIC PAF RECEPTOR

We sought to determine the effect of exogenously administered platelet -activating factor (PAF) on eicosanoid release from the left colon of the rabbit. Using an isolated buffer-perfused rabbit left colon prepar ation, 1.0- or 5.0-mu g doses of PAF were infused into the inferior me senteric artery. Effluents from the inferior mesenteric vein and colon ic lumen were collected and the concentrations of the eicosanoids, pro staglandin E, 6-ketoprostaglandin F-1 alpha, thromboxane B-2, and leuk otriene B-4 (LTB(4)), were measured by ELISA. During PAF infusion ther e was a significant increase of all prostanoids, but not LTB(4) into t he venous effluent and colonic luminal perfusate when compared to cont rol experiments. Additional studies were performed by pretreating the colons with the PAF antagonists WEB-2170 or alprazolam prior to PAF in fusion. Both venous and luminal effluent prostanoid release was effect ively blocked by WEB-2170, but not by alprazolam. Colons pretreated wi th WEB-2170 prior to PAF had markedly diminished tissue injury when co mpared to colons treated with PAF alone. Inhibition of PAF-stimulated prostanoid release by WEB-2170 suggests that a PAF-sensitive receptor is present in rabbit colonic tissue which may induce eicosanoid-mediat ed tissue injury. (C) 1995 Academic Press, Inc.