Functional effects of polyamines via activation of human β1-and β2-adrenoceptors stably expressed in CHO cells

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 β1-and β2-adrenoceptors and the functional consequences of such an interaction. chinese hamster ovary (cho) cells stably transfected with human β1-and β2-adrenoceptors were used to evaluate the effect of polyamines binding to β-adrenoceptors,campproduction and morphological changes,which were pharmacologically validated by investigating the effects of the β-adrenoceptor agonists,isoproterenol and salbutamol. polyamines interacted with human β1-and β2-adrenoceptors,as shown by the displacement of [125i]iodocyanopindolol in the binding assay. putrescine showed higher affinity to β1-than β2-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 β1-and β2-adrenoceptors,eliciting morphological changes. these findings may be of importance in physiology and in diseases involving β-adrenoceptor functionality. © 2010 by institute of pharmacology polish academy of sciences.