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Evidence for a colonic PAF receptor
W E Longo1, J D Carter, B Chandel
1Surgical Research Institute, St. Louis University School of Medicine, Missouri 63110.
Abstract:
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.
Insights
Platelet-activating factor (PAF) significantly increases prostanoid release in rabbit colons, causing tissue injury. A PAF antagonist, WEB-2170, blocked this release and reduced injury, indicating a role for PAF receptors in colonic inflammation.
Area of Science:
- Gastroenterology
- Pharmacology
- Inflammation Research
Background:
- Platelet-activating factor (PAF) is a potent inflammatory mediator.
- Eicosanoids play a crucial role in inflammatory processes within the gastrointestinal tract.
Purpose of the Study:
- To investigate the impact of exogenous platelet-activating factor (PAF) on eicosanoid release from the rabbit left colon.
- To determine the efficacy of PAF antagonists in blocking PAF-induced eicosanoid release and subsequent tissue injury.
Main Methods:
- Isolated buffer-perfused rabbit left colon preparation.
- Infusion of PAF (1.0 or 5.0 µg) into the inferior mesenteric artery.
- Measurement of prostaglandin E, 6-ketoprostaglandin F1α, thromboxane B2, and leukotriene B4 (LTB4) in venous and luminal effluents using ELISA.
- Administration of PAF antagonists (WEB-2170 or alprazolam) prior to PAF infusion.
Main Results:
- PAF infusion significantly increased prostanoid levels in venous and luminal effluents compared to controls.
- Leukotriene B4 (LTB4) levels were not significantly affected by PAF.
- WEB-2170, but not alprazolam, effectively blocked PAF-induced prostanoid release.
- WEB-2170 pretreatment significantly reduced PAF-induced colonic tissue injury.
Conclusions:
- A PAF-sensitive receptor is present in rabbit colonic tissue.
- PAF stimulates prostanoid release, contributing to colonic tissue injury.
- WEB-2170 demonstrates potential as a therapeutic agent by inhibiting PAF-mediated inflammatory responses in the colon.