Back to Search
Start Over
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.
- 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.
- Subjects :
- Adenylyl Cyclases metabolism
Adrenergic beta-Agonists metabolism
Adrenergic beta-Agonists pharmacology
Adrenergic beta-Antagonists metabolism
Animals
Cardiotonic Agents pharmacology
Chromatography, High Pressure Liquid
Cyclic AMP metabolism
Dihydroalprenolol metabolism
Eflornithine pharmacology
Enzyme Inhibitors pharmacology
Heart Atria drug effects
Isoproterenol pharmacology
Male
Membranes enzymology
Membranes metabolism
Myocardium enzymology
Myocardium metabolism
Putrescine metabolism
Rats
Rats, Wistar
Spermidine pharmacology
Spermine pharmacology
Heart drug effects
Putrescine pharmacology
Receptors, Adrenergic, beta physiology
Subjects
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