CHARACTERIZATION OF KININ RECEPTORS BY BIOASSAYS

1. Using the classical pharmacological criteria recommended by Schild, namely the order of potency of selective agonists (e.g., bradykinin, desArg(9)-bradykinin, [Hyp(3)]BK and [Aib(7)]BK) and the apparent affi nity of competitive antagonists (e.g., DArg[Hyp(3), DPhe(7), Leu(8)]BK and WIN 64338), we have attempted to characterize B-2 receptor subtyp es. It has been shown that vascular tissues (e.g., dog carotid and ren al arteries, rabbit jugular vein and rabbit aorta) are very sensitive to kinin agonists and antagonists (pD(2) and pA(2) values for BK and H OE 140 on B-2 receptors are 8.5-10.1 and 9.2-9.4, respectively, and fo r desArg(9)BK and desArg(9)[Leu(8)]BK on B-1 receptors they are 7.3-8. 6 and 7.3-7.8, respectively). Mechanisms of action of kinins differ be tween pharmacological preparations. Kinin may act directly on the smoo th muscle (e.g., rabbit jugular Vein and rabbit aorta) as well as indi rectly through other endogenous mediators such as nitric oxide (EDRF) (e.g., dog carotid and renal arteries) and prostaglandins (e.g., dog r enal artery). 2. Pharmacological analysis of rabbit jugular vein (RJV) and guinea pig ileum (GPI) has revealed different sensitivities to ce rtain synthetic analogs of BK and to competitive B-2 receptor antagoni sts between the two tissues. 3. Agonist order of potency ([Hyp(3)]BK>B K>[Aib(7)]BK) obtained for RJV differed from that obtained for GPI (BK greater than or equal to[Aib(7)]BK>[Hyp(3)]BK). Competitive antagonis ts such as DArg[Hyp(3), DPhe(7), Leu(8)]BK and WIN 64338 discriminate in favor of B-2A (RJV) and B-2B (GPI) receptor subtypes, respectively. These data demonstrate the existence of B-2 receptor subtypes. Correl ation between data obtained in the present study and those reported fo r binding to the human B-2 receptor support the view that the human re ceptor is similar to that of the rabbit.