Classification of Kinin Receptors

Abstract

AbstractThis 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 B1receptor of the rabbit aorta (rank order of potency of agonists: LysdesArg9BK > desArg9BK >= LysBK>BK; apparent affinities of antagonists Lys[Leu8]desArg9BK (pIC508.4 ) > [Leu8]desArg9BK (pIC507.4)>>>HOE 140, a B2receptor antagonist, pIC50<5.0), and the B2receptor of the rabbit jugular vein (potency of agonists: LysBK = BK>>> LysdesArg9BK = desArg9BK and HOE 140 (pIC509.0)>>>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 B1receptors (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 B2receptor 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 B2receptors. Various hypotheses are considered to interpret these findings.