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

Abstract

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). 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. 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. 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.