AJP - Heart and Circulatory Physiology, Vol 273, Issue 3 1113-H1118, Copyright © 1997 by American Physiological Society

ARTICLES

Role of Ca(2+)-independent PKC in alpha 1-adrenoceptor-mediated inotropic responses of neonatal rat hearts

X. F. Deng, S. Mulay and D. R. Varma
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

We investigated the role of protein kinase C (PKC) in alpha 1-adrenoceptor (alpha 1-AR)-mediated positive inotropic responses of neonatal rat myocardium. Bisindolylmaleimide (BIM), an inhibitor of all PKC isoforms, reduced the positive inotropic responses to phenylephrine and methoxamine but not to isoproterenol. The positive inotropic effect of phenylephrine was not attenuated by Go-6976, a selective inhibitor of Ca(2+)-dependent isoforms; it was potentiated by the 1,2-diacylglycerol kinase inhibitor R-59949. Phorbol 12,13-dibutyrate, an activator of both Ca(2+)-dependent and-independent PKC isoforms, as well as thymeleatoxin, a selective activator of Ca(2+)-dependent PKC isoforms, inhibited myocardial contractions, which were prevented by BIM and Go-6976. BIM inhibited the phenylephrine-induced increase in particulate PKC activity but not the increase in phosphatidylinositide turnover. Phenylephrine induced translocation of only Ca(2+)-independent PKC-epsilon and -delta. These results suggest that activation of Ca(2+)-independent PKC isoforms by alpha 1-AR agonists plays a key role in alpha 1-AR-mediated positive inotropic effect on neonatal myocardium.

This article has been cited by other articles:

				F. D Russell and P. Molenaar Investigation of signaling pathways that mediate the inotropic effect of urotensin-II in human heart Cardiovasc Res, September 1, 2004; 63(4): 673 - 681. [Abstract] [Full Text] [PDF]

				G. O. Andersen, E. Qvigstad, I. Schiander, H. Aass, J.-B. Osnes, and T. Skomedal alpha 1-AR-induced positive inotropic response in heart is dependent on myosin light chain phosphorylation Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1471 - H1480. [Abstract] [Full Text] [PDF]

				Z.-W. Yang, J. Wang, T. Zheng, B. T. Altura, and B. M. Altura Importance of PKC and PI3Ks in ethanol-induced contraction of cerebral arterial smooth muscle Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2144 - H2152. [Abstract] [Full Text] [PDF]

				Z.-W. Yang, J. Wang, T. Zheng, B. T. Altura, and B. M. Altura Low [Mg2+]o induces contraction and [Ca2+]i rises in cerebral arteries: roles of Ca2+, PKC, and PI3 Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2898 - H2907. [Abstract] [Full Text] [PDF]

				C. M. Liedtke and T. S. Cole Antisense oligonucleotide to PKC-epsilon alters cAMP-dependent stimulation of CFTR in Calu-3 cells Am J Physiol Cell Physiol, November 1, 1998; 275(5): C1357 - C1364. [Abstract] [Full Text] [PDF]

				X.-F. Deng, A. Sculptoreanu, S. Mulay, K. G. Peri, J.-F. Li, W.-H. Zheng, S. Chemtob, and D. R. Varma Crosstalk between Alpha-1A and Alpha-1B Adrenoceptors in Neonatal Rat Myocardium: Implications in Cardiac Hypertrophy J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 489 - 496. [Abstract] [Full Text]