Putrescine modulation of acute activation of the β-adrenergic system in the left atrium of rat

Abstract

Endogenous polyamines mediate acute metabolic effects and cardiac hypertrophy associated to β-adrenoceptor stimulation. The aim of this study is to characterize the role of polyamines on β-adrenoceptor system mediated responses. To this end, the functional interaction of polyamine modifying drugs on isoproterenol-elicited cardiotonic effect, in isolated left atria of male Wistar rats, and their effects on [3H]dihydroalprenolol (DHA) binding on β-adrenoceptors and on adenylyl cyclase activity of membrane heart were studied. Polyamines interact with β-adrenoceptors in rat heart, as shown by the displacement of [3H]DHA binding. Furthermore, putrescine (but not spermidine or spermine) increased adenylyl cyclase activity, elicited a positive inotropism and increased intracellular cAMP. The putrescine effect on adenylyl cyclase was not antagonized by the β-adrenoceptors blockers, alprenolol and ICI-118,551, and facilitated the isoproterenol effect. Neither alprenolol, atenolol nor ICI-118,551 antagonized putrescine-elicited positive inotropism.However, the effectwas abolished in preparations with desensitized β-adrenoceptors. α-Difluoromethylornithine, an inhibitor of ornithine decarboxylase, antagonized the effect of isoproterenol on inotropism and cAMP increase. In addition, putrescine might elicit effects by mechanisms independent of β-adrenoceptor system, since in left atria with functional desensitized receptors an interactionwith ouabain-elicited cardiotonic effectwas observed. These results suggest that putrescine may act as a lowaffinity agonist on β-adrenoceptors and modulate acute responses mediated by β-adrenoceptors. These findings may be of importance in the physiology and in diseases involving cardiac β-adrenoceptors.