The effects of bradykinin agonists and antagonists on visceral polymodal receptor activities

Abstract

The endogenous algesic agent bradykinin (BK) is a consistent stimulant for the polymodal receptor, a type of nociceptor. Two types of BK receptor, B1 and B2, have been proposed in smooth muscles by Regoli. The type of BK receptor mediating the BK response of the polymodal receptor was studied using 3 BK analogs, des-Arg⁹-BK (a Bl agonist), des-Arg⁹-[Leu⁸]-BK (a Bl antagonist), and [Thi^5,8, d-Phe⁷]-BK (a B2 antagonist). Single- and multi-fiber activities from testicular polymodal receptors were recorded in vitro using testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Neither des-Arg⁹-BK, des-Arg⁹-[Leu⁸]-BK, nor [Thi^5,8,d-Phe⁷]-BK induced discharges in nociceptors at concentrations up to 9.4 × 10⁻⁶ M. Des-Arg⁹-[Leu⁸]-BK (up to 9.4 × 10⁻⁶ M) did not suppress responses to BK (9.4 × 10⁻⁸˜⁻⁹M), whereas [Thi^5,8,d-Phe⁷]-BK (above 2.8 × 10^-7 M) suppressed the BK response in a concentration-dependent manner and shifted the concentration-response curve of BK to the right. It was ascertained that [Thi^5,8,d-Phe⁷]-BK had no effect on responses to noxious heat and high K⁺ solution. These results suggest that the BK receptor mediating the nociceptor response to BK is of the B2 type.