Role of beta 1- and beta 2-adrenoceptors in hypertrophic and apoptotic effects of noradrenaline and adrenaline in adult rat ventricular cardiomyocytes.
In adult rat ventricular cardiomyocytes alpha1-adrenoceptor (AR) stimulation causes increases in protein synthesis. On the other hand beta1-AR stimulation inhibits protein synthesis, and evokes apoptotic cell death. We studied, in adult rat ventricular cardiomyocytes, effects of noradrenaline (NA), adrenaline (ADR) and phenylephrine (PE) on protein synthesis (assessed by [3H]-phenylalanine incorporation into the cardiomyocytes) in relation to effects on early apoptosis (measured by Annexin V/propidium iodide staining). PE (10(-9)-10(-5) M) induced protein synthesis was not affected by the beta1-AR blocker CGP 20712A (CGP, 300 nM) or beta2-AR blocker ICI 118,551 (ICI, 55 nM). ADR (10(-9)-10(-5) M) induced protein synthesis was enhanced by CGP and decreased by ICI. Pretreatment of the cardiomyocytes with pertussis toxin (PTX) decreased NA- and ADR- induced protein synthesis, but did not affect PE-effects. NA (10(-5) M) and ADR (10(-5) M) caused a significant increase in the number of apoptotic cells; these effects were enhanced by PTX-treatment, abolished by CGP, but not significantly affected by ICI. Furthermore, there was a significant negative correlation between catecholamine-evoked apoptosis and catecholamine-induced hypertrophic effects. We conclude that, in ventricular cardiomyocytes of adult rats, growth-promoting effects of NA and ADR are composed of alpha1A-AR mediated increase in protein synthesis and beta1-AR mediated apoptosis that counteracts increases in protein synthesis. The role of beta2-adrenoceptor appears to be a balance of antiapoptotic effects via a PTX-sensitive pathway and proapoptotic effects via a GS-adenylyl cyclase pathway.
Pönicke
Klaus
K
Institute of Pharmacology, University of Halle, 06097 Halle (Saale), Germany.
Heinroth-Hoffmann
Ingrid
I
Brodde
Otto-Erich
OE
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D016276:Ventricular Function
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D009638:Norepinephrine; D004837:Epinephrine