Polyphloretin phosphate reduces the algesic action of bradykinin by interfering with E-type prostaglandins

(1) The method of the isolated perfused rabbit ear connected to the body by its nerve only was used to investigate the influence of the prostaglandin-antagonist polyphloretin phosphate (PPP) on the algesic effect of bradykinin (B) and acetylcholine (ACh). (2) Intra-arterial injections of B and ACh into the ear elicit a reflex fall in systemic blood pressure of the anaesthetized animal. PPP reduces this effects of B in proportion to the dose. The effect of ACh is reduced only to a small extent and only under higher concentrations of PPP than those necessary for inhibiting the effect of B. (3) Prostaglandin E1 (PGE1), when infused i.a. into the ear, enhances the effect of B and ACh by a sensitizing action on the perivascular pain receptors. PPP reduces or totally abolishes the PGE1-induced enhancement of the effect of B and ACh. (4) It is concluded that PPP reduces the effect of B mainly by inhibiting directly the pain enhancing action of the endogenously released PGs of the E-type. The effect of ACh is reduced only in the high concentration of PPP to a small extent probably by inhibiting the ACh-action rather than the sensitizing action of the only minimal released amounts of PGs. The PG-antagonizing action of PPP is further proven by the fact that during an additional infusion of PGE1 the enhanced effects of both B as well as ACh are reduced or abolished by PPP.