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, B1 and B2, mediating contraction of the rabbit aorta (B1) and the rabbit jugular vein (B2). Studies on dog vessels contributed to the identification of B2 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 B2 receptors in endothelia and in the smooth muscle, mediating relaxation through NO (endothelia) and prostanoids (smooth muscle). B1 receptors that relax renal arterial smooth muscle through the release of prostanoids were also identified. In other vessels, B2 receptors may also mediate smooth muscle contraction. Recent studies in human vessels (umbilical vein) have confirmed the existence of contractile B1 and B2 receptors in venous smooth muscles. B1 and B2 receptors have been cloned; molecular biology has provided the reference data for comparison with findings of classical pharmacology and binding assays. Similarities and differences in B1 and B2 receptors between human and animal tissues demonstrate the heterogeneity (related to species) of kinin B2 and B1 receptors and confirm the findings of early classical pharmacological experiments.
Regoli
D
D
Department of Pharmacology, Medical School, Université de Sherbrooke, Québec, Canada.
Pheng
L H
LH
Allogho
S N
SN
Nguyen-Le
X K
XK
Gobeil
F
F
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D008967:Molecular Biology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011817:Rabbits; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology; D014680:Veins / Q000378:metabolism
D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin