Prostaglandin F2alpha reduces the algesic effect of bradykinin by antagonizing the pain enhancing action of endogenously released prostaglandin E.
1 The isolated perfused ear of the rabbit connected to the body only by its nerve, was used to investigate the influence of prostaglandin F2alpha on the algesic effect of bradykinin and acetylcholine. 2 Bradykinin and acetylcholine, following intra-arterial injection into the isolated perfused ear elicited a dose-related reflex fall in blood pressure due to stimulation of paravascular pain receptors (= algesic effect). 3 Infusion of prostaglandin F2alpha (0.1 to 1 ng/ml) into the rabbit ear reduced the algesic effect of bradykinin but not that of acetylcholine. 4 The onset of the reflex fall in blood pressure by bradykinin but not that by acetylcholine was delayed by infusion of prostaglandin F2alpha into the ear. 5 Infusion of prostaglandin E1 into the rabbit ear led to an enhancement of the algesic effect of bradykinin and acetylcholine. Enhancement of both effects was abolished by infusion of prostaglandin F2alpha. 6 During inhibition of the endogenous synthesis of prostaglandins (mainly E-type) by indomethacin, a low concentration of prostaglandin F2alpha no longer reduced the algesic effect of bradykinin. However, a high concentration of F2alpha continued to enhance the effect of bradykinin and acetylcholine. 7 Prostaglandin F2alpha influenced neither the brief reduction in venous outflow produced by bradykinin nor the brief increase in venous outflow caused by acetylcholine. 8 The results suggest that prostaglandin F2alpha does not directly reduce the effect of bradykinin but inhibits the enhancement of its algesic effect produced by prostaglandin E that is released endogenously by bradykinin. That the algesic effect of acetylcholine is not reduced by prostaglandin F2alpha is in keeping with its releasing very little endogenous prostaglandin E.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D004423:Ear / Q000098:blood supply; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D011458:Prostaglandins E / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D011460:Prostaglandins F / Q000494:pharmacology*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014666:Vasomotor System / Q000187:drug effects
D011458:Prostaglandins E; D011460:Prostaglandins F; D000109:Acetylcholine; D001920:Bradykinin; D007213:Indomethacin