Anti-apoptotic effects of muscarinic receptor activation are mediated by Rho kinase

Activation of muscarinic receptors has been shown to be neuroprotective in several different models of apoptosis, but the mechanism of this action is unknown. Therefore, we investigated the intermediate signals mediating the anti-apoptotic action of muscarinic receptor activation in SH-SY5Y cells. Inhibition of most muscarinic receptor-coupled actions had no effect on protection, but inhibition of Rho kinase with HA-1077 concentration-dependently was able to completely block the protection against H2O2- and camptothecin-induced apoptosis produced by stimulation of muscarinic receptors. These results demonstrate that the anti-apoptotic effect provided by muscarinic receptor stimulation is dependent on the activity of Rho kinase.