AHEART May 45/5

Schlüter, Klaus-Dieter, Andreas Simm, Matthias Schäfer, Gerhild Taimor, and Hans Michael Piper. Early response kinase and PI 3-kinase activation in adult cardiomyocytes and their role in hypertrophy. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H1655–H1663, 1999.—The present study investigated the role of early response kinase (ERK) and phosphatidylinositol 3 (PI 3)-kinase in ventricular cardiomyocytes from adult rat for the hypertrophic response to a-adrenoceptor stimulation. Parameters of the hypertrophic response were stimulation of protein synthesis and induction of creatine kinase BB. The a-adrenoceptor agonist phenylephrine (10 μmol/l) activated ERK2 and PI 3-kinase. The protein kinase C inhibitor bisindolylmaleimide (5 μmol/l) and the mitogen-activated protein kinase kinase inhibitor PD-98059 (10 μmol/l) but not the tyrosine kinase inhibitor genistein (100 μmol/l) blocked ERK2 activation. Inhibition of ERK2 activation abolished induction of creatine kinase BB by phenylephrine but not the increase in protein synthesis. The PI 3-kinase inhibitor wortmannin (100 nmol/l) blocked protein synthesis under a-adrenoceptor stimulation but did not interfere with ERK2 activation. Inhibition of the ERK2 pathway with PD-98059 did not affect PI 3-kinase activation. We conclude that ERK2and PI 3-kinase-dependent pathways represent two mutually exclusive ways of signaling that lead to different aspects of the hypertrophic response to a-adrenoceptor stimulation.