Identification of B(2)-bradykinin receptors in guinea pig brain regions, spinal cord and peripheral tissues.

The aim of this study was to characterize the biochemical and pharmacological properties of bradykinin receptors in the guinea pig central and peripheral tissues using radioligand binding techniques. Specific [(3)H]bradykinin ([(3)H]BK) receptor binding to homogenates of guinea pig cerebral cortex, hippocampus, spinal cord, ileum, kidney, heart, vas deferens and uterus was of high affinity, saturable and reversible. Scatchard analysis of saturation (0.005-1 nM) data revealed the presence of a single population of non-interacting nanomolar affinity (generally 0.14-0.38 nM) binding sites in all these tissues, with the ileum having the highest affinity (K(D) = 0.02 nM) and the greatest density of sites (B(max) = 5.8 +/- 1.8 pmol/g tissue). The rank order of tissue enrichment in terms of [(3)H]BK binding sites was: ileum > uterus > kidney > heart > vas deferens > spinal cord > cerebral cortex > hippocampus. Unlabelled BK and its analogs inhibited [(3)H]BK binding in the above tissues in a concentration-dependent manner and with the same rank order of potency: BK > Lys-BK > Met-Lys-BK > [ d -Arg (0)-Hyp (3)- d -Phe (7)]BK ? [ d -Arg (0)-Hyp (3)-Thi (5,8)- d -Phe (7)]BK ? Des-Arg (9)-BK . A similar rank order of potency of agonists was observed for their ability to contract guinea pig uterine and ileal smooth muscle strips. The pharmacological profile of [(3)H]BK receptor binding, using BK agonists and antagonists, and that of functional responses was consistent with the identification of BK receptors of the B(2)-type in the guinea pig central nervous system and peripheral tissues.