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 H(2)O(2)- 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.
De Sarno
Patrizia
P
Department of Psychiatry and Behavioral Neurobiology, 1720 Seventh Avenue South, Sparks Center 1057, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
Shestopal
Svetlana A
SA
Zmijewska
Anna A
AA
Jope
Richard S
RS
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D043587:Receptor, Muscarinic M3; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil