RECEPTORS FOR KININS - FROM CLASSICAL PHARMACOLOGY TO MOLECULAR-BIOLOGY

In the past twenty years, we have focused our efforts on the study of kinin receptors involved in contraction or relaxation of vascular smoo th muscle. Initial studies on rabbit vessels led to the discovery of t wo kinin receptors, B-1 and B-2, mediating contraction of the rabbit a orta (B-1) and the rabbit jugular vein (B-2). Studies on dog vessels c ontributed to the identification of B-2 receptors in arterial endothel ium 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 re laxation 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 m ay also mediate smooth muscle contraction. Recent studies in human ves sels (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 for co mparison with findings of classical pharmacology and binding assays. S imilarities 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 classica l pharmacological experiments.