Renal bradykinin and vasopressin receptors: Ligand selectivity and classification

We studied the specific binding of radiolabeled bradykinin ([³H]BK) and vasopressin ([³H]AVP) to membrane preparations of bovine and porcine kidney medulla. [³H]BK reversibly labeled a single site (K(d) = 1.06 nM) in bovine kidney medulla independently of [Mg²⁺]. The number of BK receptors in bovine kidney medulla, B(max) = 122 fmol/mg protein, is markedly (2- to 3-fold) higher than that reported in other tissues. Further characterization by ligand binding indicated that the bovine bradykinin receptor was the B(2a) subtype, pharmacologically related to B(2a) receptors expressed by human and rabbit tissues. In contrast, the specific binding of [³H]BK, but not [³H]AVP, to porcine kidney medulla (K(d) = 0.32 nM, B(max) = 45 fmol/mg) was dependent upon the presence of enzyme inhibitors to prevent the rapid and selective degradation of bradykinin. Interspecies differences were revealed for renal medulla V₂ vasopressin receptors with respect to their abundance and their affinity for several V₂-selective ligands. In summary, (i) bovine kidney medulla is a convenient source of tissue for studying the B(2a) bradykinin receptor subtype; (ii) there are significantly species- dependent differences in both the abundance of renal medulla B(2a) and V₂ receptors and the ligand selectivity of V₂ receptors; and (iii) these findings are significant in relation to the physiological and pathological roles of renal kinins and their interaction with the neurohypophysial peptide hormone system.