CENTRAL B-2 RECEPTOR INVOLVEMENT IN THE ANTINOCICEPTIVE EFFECT OF BRADYKININ IN RATS

1 The effect of intracerebroventricular (i.c.v.) injection of bradykin in (BK) and related peptides was tested on the dental pulp electrical stimulation threshold (DPEST) in rats. 2 BK (4, 8 and 16 nmol) induced a dose-dependent increase of DPEST, indicative of an antinociceptive effect. 3 I.c.v. injection of equimolar doses of BK-related peptides, Lys-BK and Met-Lys-BK, also induced an increase of DPEST, but the magn itude of the effect was not as intensive as that induced by BK, when t he maximum increase of DPEST was considered. The peptide T-kinin induc ed a short lasting and weak antinociceptive effect. 4 The B-1 agonist, des-Arg(9)-BK (8 nmol) induced a significant antinociceptive effect, but this was not as intensive as that induced by BK. 5 The B-2 antagon ist D-Arg(0)-Hyp(3)-Thi(5,8)-D-Phe(7)-BK (D-Arg(0)) competitively anta gonized the BK-induced antinociception. Likewise, Hyp(3)-Thi(5,8)-D-Ph e(7)-BK (Hyp) also antagonized BK effect. However, the compound Thi(5, 8)-D-Phe(7)-BK (Thi), initially considered a pure BK antagonist, induc ed an antinociceptive effect, supporting previous observations that th is peptide can also act as a partial agonist. 6 It is concluded that t he dose-dependent antinociceptive effect induced by i.c.v. injection o f BK is mediated by the stimulation of brain B-2 receptors.