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 preparation, 1.0- or 5.0-micrograms doses of PAF were infused into the inferior mesenteric artery. Effluents from the inferior mesenteric vein and colonic lumen were collected and the concentrations of the eicosanoids, prostaglandin E, 6-ketoprostaglandin F1 alpha, thromboxane B2, and leukotriene B4 (LTB4), were measured by ELISA. During PAF infusion there was a significant increase of all prostanoids, but not LTB4 into the venous effluent and colonic luminal perfusate when compared to control experiments. Additional studies were performed by pretreating the colons with the PAF antagonists WEB-2170 or alprazolam prior to PAF infusion. Both venous and luminal effluent prostanoid release was effectively blocked by WEB-2170, but not by alprazolam. Colons pretreated with WEB-2170 prior to PAF had markedly diminished tissue injury when compared 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-mediated tissue injury.
Longo
W E
WE
Surgical Research Institute, St. Louis University School of Medicine, Missouri 63110.
Carter
J D
JD
Chandel
B
B
Niehoff
M
M
Standeven
J
J
Deshpande
Y
Y
Vernava
A M
AM
Polites
G
G
Kulkarni
A D
AD
Kaminski
D L
DL
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015777:Eicosanoids / Q000378:metabolism; D066298:In Vitro Techniques; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D015777:Eicosanoids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C063964:bepafant