title: Putrescine modulation of acute activation of the beta-adrenergic system in the left atrium of rat.
abstract: Endogenous polyamines mediate acute metabolic effects and cardiac hypertrophy associated to beta-adrenoceptor stimulation. The aim of this study is to characterize the role of polyamines on beta-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 [(3)H]dihydroalprenolol (DHA) binding on beta-adrenoceptors and on adenylyl cyclase activity of membrane heart were studied. Polyamines interact with beta-adrenoceptors in rat heart, as shown by the displacement of [(3)H]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 beta-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 effect was abolished in preparations with desensitized beta-adrenoceptors. alpha-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 beta-adrenoceptor system, since in left atria with functional desensitized receptors an interaction with ouabain-elicited cardiotonic effect was observed. These results suggest that putrescine may act as a low affinity agonist on beta-adrenoceptors and modulate acute responses mediated by beta-adrenoceptors. These findings may be of importance in the physiology and in diseases involving cardiac beta-adrenoceptors.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Bordallo
authors.forename: Begoña
authors.initials: B
authors.lastname: Cantabrana
authors.forename: Lucía
authors.initials: L
authors.lastname: Velasco
authors.forename: Lorena
authors.initials: L
authors.lastname: Secades
authors.forename: Clara
authors.initials: C
authors.lastname: Meana
authors.forename: Miriam
authors.initials: M
authors.lastname: Méndez
authors.forename: Javier
authors.initials: J
authors.lastname: Bordallo
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez