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

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

Authors :
Bordallo C
Cantabrana B
Velasco L
Secades L
Meana C
Méndez M
Bordallo J
Sánchez M
Source :
European journal of pharmacology [Eur J Pharmacol] 2008 Nov 19; Vol. 598 (1-3), pp. 68-74. Date of Electronic Publication: 2008 Aug 13.
Publication Year :
2008

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.

Details

Language :
English
ISSN :
0014-2999
Volume :
598
Issue :
1-3
Database :
MEDLINE
Journal :
European journal of pharmacology
Publication Type :
Academic Journal
Accession number :
18755180
Full Text :
https://doi.org/10.1016/j.ejphar.2008.07.069