Classification of Kinin Receptors

Abstract

This minireview is divided into three parts: the first part refers to the characterization and classification of kinin receptors using agonists and antagonists in isolated tissues (classical pharmacology). Two kinin receptors have been considered on the basis of their distinct pharmacology, namely the B₁ receptor of the rabbit aorta (rank order of potency of agonists: LysdesArg⁹BK > desArg⁹BK >= LysBK>BK; apparent affinities of antagonists Lys[Leu⁸]desArg⁹BK (pIC₅₀ 8.4 ) > [Leu⁸]desArg⁹BK (pIC₅₀ 7.4)>>>HOE 140, a B₂ receptor antagonist, pIC₅₀<5.0), and the B₂ receptor of the rabbit jugular vein (potency of agonists: LysBK = BK>>> LysdesArg⁹BK = desArg⁹BK and HOE 140 (pIC₅₀ 9.0)>>>Lys[Leu⁸]desArg⁹BK, pIC₅₀<5.0). The second part describes speciesrelated B₁receptor subtypes, demonstrated by different pharmacological profiles of agonists and antagonists: human, rabbit and pig subtypes (LysdesArg⁹BK >> desArg⁹B K and Lys[Leu⁸]desArg⁹BK > [Leu⁸]desArg⁹BK) and dog, rat, mouse and hamster B₁ receptors (desArg⁹BK = LysdesArg⁹BK and [Leu⁸]desArg⁹BK = Lys[Leu⁸]desArg⁹BK). Affinities of agonists and antagonists in some species (man, rabbit, pig) are significantly increased (at least 10-fold) by the presence of a Lys at their Nterminus. The last part describes species-related B₂ receptor subtypes supported by results obtained with non-peptide receptor agonists (FR 190997) and antagonists (FR 173657). While BK acts as a full agonist in man, rabbit and pig, FR 190997 behaves as a full agonist on human, as partial agonist on rabbit, and as pure antagonist on pig B₂ receptors. Various hypotheses are considered to interpret these findings.