RT info:eu-repo/semantics/article
T1 Functional effects of polyamines via activation of human β1- and β2 -adrenoceptors stably expressed in CHO cells
A1 Meana, Clara
A1 Bordallo, Javier
A1 Bordallo, Carmen
A1 Suárez, Lorena
A1 Cantabrana, Begoña
A1 Sánchez, Manuel
AB Polyamines mediate acute metabolic effects and cardiac hypertrophy associated with β-adrenoceptor stimulation. They may also modulate β-adrenoceptors, causing functional responses in rat atria and tracheal smooth muscle. The aim of this study was to determine whether polyamines interact with human β(1)- and β(2)-adrenoceptors and the functional consequences of such an interaction. Chinese hamster ovary (CHO) cells stably transfected with human β(1)- and β(2)-adrenoceptors were used to evaluate the effect of polyamines binding to β-adrenoceptors, cAMP production and morphological changes, which were pharmacologically validated by investigating the effects of the β-adrenoceptor agonists, isoproterenol and salbutamol. Polyamines interacted with human β(1)- and β(2)-adrenoceptors, as shown by the displacement of [(125)I]iodocyanopindolol in the binding assay. Putrescine showed higher affinity to β(1)- than β(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 β-blocker. A 10 to 15 h incubation with putrescine produced a spindle-like form and spatial organization via β-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 β-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 β(1)- and β(2)-adrenoceptors, eliciting morphological changes. These findings may be of importance in physiology and in diseases involving β-adrenoceptor functionality.
SN 1734-1140
YR 2010
FD 2010
LK https://uvadoc.uva.es/handle/10324/74262
UL https://uvadoc.uva.es/handle/10324/74262
LA eng
NO Pharmacological Reports, julio 2010, vol. 62, n.4, p. 696-706
DS UVaDOC
RD 29-ene-2025