RECEPTORS FOR KININS - FROM CLASSICAL PHARMACOLOGY TO MOLECULAR-BIOLOGY

in the past 20 years, we have focused our efforts on the study of kini n receptors involved in contraction or relaxation of vascular smooth m uscle. Initial studies on rabbit vessels led to the discovery of two k inin receptors, B-1 and B-2 mediating contraction of the rabbit aorta (B-1) and the rabbit jugular vein (B-2). Studies on clog vessels contr ibuted to the identification of B-2 receptors in arterial endothelium promoting the release of NO and the relaxation of arterial smooth musc les; further studies on dog renal vessels led to the demonstration of B-2 receptors in endothelia and in the smooth muscle, mediating relaxa tion through NO (endothelia) and prostanoids (smooth muscle). B-1 rece ptors that relax renal arterial smooth muscle through the release of p rostanoids were also identified. In other vessels, B-2 receptors may a lso mediate smooth muscle contraction. Recent studies in human vessels (umbilical vein) have confirmed the existence of contractile B-1 and B-2 receptors in venous smooth muscles. B-1 and B-2 receptors have bee n cloned; molecular biology has provided the reference data far compar ison with findings of classical pharmacology and binding assays. Simil arities and differences in B-1 and B-2 receptors between human and ani mal tissues demonstrate the heterogeneity (related to species) of kini n B-2 and B-1 receptors and confirm the findings of early classical ph armacologic experiments.