The alpha(1)-adrenoreceptor-induced positive inotropic effect in rat and human heart tissue is dependent on myosin light chain kinase phosphorylation, being reduced by approximately 90% by MLCK inhibition.
The positive inotropic effect of alpha(1)-adrenergic receptor stimulation in cardiac muscle is dependent on myosin light chain kinase phosphorylation.
The possible involvement of different kinases in the alpha(1)-adrenoreceptor (AR)-mediated positive inotropic effect (PIE) was investigated in rat papillary muscle and compared with beta-AR-, endothelin receptor- and phorbol ester-induced changes in contractility. The alpha(1)-AR-induced PIE was not reduced by the inhibitors of protein kinase C (PKC), MAPK (ERK and p38), phosphatidyl inositol 3-kinase, or calmodulin kinase II. However, PKC inhibition attenuated the effect of phorbol 12-myristate 13-acetate (PMA) on contractility. alpha(1)-AR-induced PIE was reduced by approximately 90% during inhibition of myosin light chain kinase (MLCK) by 1-(5-chloronaphthalene-1-sulfonyl)1H-hexahydro-1,4-diazepine (ML-9). Endothelin-induced PIE was also reduced by ML-9, but ML-9 had no effect on beta-AR-induced PIE. The Rho kinase inhibitor Y-27632 also reduced the alpha(1)-AR-induced PIE. The alpha(1)-AR-induced PIE in muscle strips from explanted failing human hearts was also sensitive to MLCK inhibition. alpha(1)-AR induced a modest increase in (32)P incorporation into myosin light chain in isolated rat cardiomyocytes. This effect was eliminated by ML-9. The PIE of alpha(1)-AR stimulation seems to be dependent on MLCK phosphorylation.
Andersen et al. (Tue,) conducted a other in Heart failure (human samples) / normal (rat samples). alpha(1)-AR stimulation and kinase inhibitors (e.g., ML-9, Y-27632) vs. beta-AR, endothelin receptor, and phorbol ester stimulation was evaluated on Positive inotropic effect (PIE) and myosin light chain phosphorylation. The alpha(1)-adrenoreceptor-induced positive inotropic effect in rat and human heart tissue is dependent on myosin light chain kinase phosphorylation, being reduced by approximately 90% by MLCK inhibition.