Activation of p70S6Kinase byβ-adrenoceptor Agonists on Adult Cardiomyocytes

Cardiac cellular hypertrophy plays an important role in cardiovascular diseases. Up until now, little has been known about the regulation of cellular growth on the level of intracellular signalling. Here, the implication of the p70S6-kinase (p70S6K) in the hypertrophic response afterβ-adrenergic stimulation of cardiac myocytes from adult rats was investigated. Isoproterenol stimulation can activate p70S6Kin adult cardiomyocytes analysed by direct kinase assays and retarded gel mobility. This signalling ofβ-adrenoceptor stimulation is found only under conditions where the cardiomyocytes exhibit also a hypertrophic response toβ-adrenoceptor stimulation as measured by increase in protein content, RNA content and incorporation of radiolabelled amino acids. Rapamycin, a specific inhibitor of this kinase, reduces the trophic responses to control levels, suggesting an involvement of the p70S6-kinase in the development of cellular hypertrophy. An engagement of the MAP-kinase (ERK-1/2) pathway in the β-adrenergic induced growth of cardiac myocytes from adult rats was excluded.