An α-adrenoceptor inhibitory action of kynuramine

Abstract

Kynuramine, an endogenously occuring amine, inhibited the vasoconstrictor responses to norepinephrine in the isolated perfused mesentric arteries of rats and blocked the relaxation of rabbit intestinal smooth muscle by phenylephrine. Similarly, kynuramine reversed clonidine-induced inhibition of the cholinergic twitch response in the guinea-pig ileum. These effcets, seen with concentrations ranging from 4 to 60 μg/ml, aer consistent with an α-adrenoceptor inhibitory action of kynuramine at both presynaptic sites. Kynuramine itself, lacked intrinsic activity on α-adrenoceptors and showed a complete lack of affinity for β-adrenoceptors in the rabbit intestine and guinea pig tracheal chain preparation. None of the effects of kynuramine could be attributed to the formation of 4-hydroxyquinoline, the deaminated metabolite of kynuramine. Additionally, no evidence was obtained for an action on muscarinic receptors or non-specific effects on vascular smooth muscle. However, a slight, transient stimulant action was evident on intestinal smooth muscle. It is concluded tha kynuramine inhibits both presynaptic and postsynaptic α-adrenoceptors in vitro and it is conceivable that the compound might function as an endogenous inhibitor of α-adrenoceptors in vivo.