Functional effects of polyamines via activation of human beta1- and beta2-adrenoceptors stably expressed in CHO cells.

Article Details

Citation
Copy to clipboard

Meana C, Bordallo J, Bordallo C, Suarez L, Cantabrana B, Sanchez M

Functional effects of polyamines via activation of human beta1- and beta2-adrenoceptors stably expressed in CHO cells.

Pharmacol Rep. 2010 Jul-Aug;62(4):696-706.

PubMed ID
20885010 [ View in PubMed
]
Abstract

Polyamines mediate acute metabolic effects and cardiac hypertrophy associated with beta-adrenoceptor stimulation. They may also modulate beta-adrenoceptors, causing functional responses in rat atria and tracheal smooth muscle. The aim of this study was to determine whether polyamines interact with human beta(1)- and beta(2)-adrenoceptors and the functional consequences of such an interaction. Chinese hamster ovary (CHO) cells stably transfected with human beta(1)- and beta(2)-adrenoceptors were used to evaluate the effect of polyamines binding to beta-adrenoceptors, cAMP production and morphological changes, which were pharmacologically validated by investigating the effects of the beta-adrenoceptor agonists, isoproterenol and salbutamol. Polyamines interacted with human beta(1)- and beta(2)-adrenoceptors, as shown by the displacement of [(125)I]iodocyanopindolol in the binding assay. Putrescine showed higher affinity to beta(1)- than beta(2)-adrenoceptors. Spermidine and spermine produced partial displacement (approximately 50%) and, at the highest concentration, the effect was reversed. Putrescine and spermine acutely increased cAMP and, in a serum-free medium, induced a stellate-like form in cells, which was inhibited by propranolol, a beta-blocker. A 10 to 15 h incubation with putrescine produced a spindle-like form and spatial organization via beta-adrenoceptor activation, evidenced by the antagonizing effect by propranolol and lack of effect in wild-type CHO cells. Additionally, it decreased cell proliferation independently of beta-adrenoceptor activation. Spermine caused cell death via fetal bovine serum-dependent and -independent mechanisms. The results suggest that putrescine may act as a non-selective and low affinity agonist of human beta(1)- and beta(2)-adrenoceptors, eliciting morphological changes. These findings may be of importance in physiology and in diseases involving beta-adrenoceptor functionality.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
PutrescineBeta-1 adrenergic receptorProteinHumans
Unknown
Not AvailableDetails
PutrescineBeta-2 adrenergic receptorProteinHumans
Unknown
Not AvailableDetails
SpermidineBeta-1 adrenergic receptorProteinHumans
Unknown
Not AvailableDetails
SpermidineBeta-2 adrenergic receptorProteinHumans
Unknown
Not AvailableDetails
SpermineBeta-1 adrenergic receptorProteinHumans
Unknown
Not AvailableDetails
SpermineBeta-2 adrenergic receptorProteinHumans
Unknown
Not AvailableDetails