Receptors for kinins: From classical pharmacology to molecular biology

in the past 20 years, we have focused our efforts on the study of kinin receptors involved in contraction or relaxation of vascular smooth muscle. Initial studies on rabbit vessels led to the discovery of two kinin 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 contributed to the identification of B-2 receptors in arterial endothelium promoting the release of NO and the relaxation of arterial smooth muscles; further studies on dog renal vessels led to the demonstration of B-2 receptors in endothelia and in the smooth muscle, mediating relaxation through NO (endothelia) and prostanoids (smooth muscle). B-1 receptors that relax renal arterial smooth muscle through the release of prostanoids were also identified. In other vessels, B-2 receptors may also 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 been cloned; molecular biology has provided the reference data far comparison with findings of classical pharmacology and binding assays. Similarities and differences in B-1 and B-2 receptors between human and animal tissues demonstrate the heterogeneity (related to species) of kinin B-2 and B-1 receptors and confirm the findings of early classical pharmacologic experiments.