KININ RECEPTOR (B-1, B-2) ANTAGONISTS AND THEIR THERAPEUTIC POTENTIAL

Physiological and pathological effects of kinins result from the activ ation of specific receptors which are present in various organs. Kinin receptors have been characterized through studies on isolated organs in vitro and have been classified as B-1 and B-2. A careful analysis o f B-2 receptors led to the identification of two subtypes, namely B-2r b (in the rabbit) and B-2gp (in the guinea-pig). The distinction betwe en B-2rb and B-2gp receptors is primarily based on differences in the activities of selective agonists and particularly on differences in af finities of competitive antagonists, namely DArg[Hyp(3), DPhe(7), Leu( 8)]BK and the non-peptide compound, WIN 64338. The non-competitive ant agonist, HOE 140, has shown the same affinity on B-2rb and B-2gp. The potential role of B-1 and B-2 receptors in physiopathology is analysed on data obtained with specific and selective antagonists of the B-1(d esArg(9)[Leu(8)]BK) and B-2 (HOE 140) receptors. The therapeutic poten tial of endogenous kinins as mediators of the therapeutic beneficial e ffects of the angiotensin-converting enzyme inhibitors or the potentia l of the use of exogenous kinins in the vascular permeability are disc ussed together with the therapeutic potential of B-1 and B-2 receptor antagonists.