Present address: Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shingawa-ku, Tokyo 142-8501, Japan
Dopamine D1 receptor signaling system regulates ryanodine receptor expression after intermittent exposure to methamphetamine in primary cultures of midbrain and cerebral cortical neurons
Version of Record online: 18 JUL 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 118, Issue 5, pages 773–783, September 2011
How to Cite
Kurokawa, K., Mizuno, K., Kiyokage, E., Shibasaki, M., Toida, K. and Ohkuma, S. (2011), Dopamine D1 receptor signaling system regulates ryanodine receptor expression after intermittent exposure to methamphetamine in primary cultures of midbrain and cerebral cortical neurons. Journal of Neurochemistry, 118: 773–783. doi: 10.1111/j.1471-4159.2011.07366.x
- Issue online: 11 AUG 2011
- Version of Record online: 18 JUL 2011
- Accepted manuscript online: 25 JUN 2011 10:49AM EST
- Received May 12, 2011; revised manuscript received June 20, 2011; accepted June 20, 2011.
- cerebral cortical neurons in primary culture;
- dopamine D1 receptors;
- protein kinase A;
- ryanodine receptors
J. Neurochem. (2011) 118, 773–783.
Regulatory mechanisms of ryanodine receptor (RyR) expression are not well known, although methamphetamine (METH) has been reported to up-regulate RyRs in mouse brain. This study investigate regulatory mechanisms of RyR expression by dopaminergic system using the midbrain and cerebral cortical neurons in primary culture intermittently exposed to METH and dopamine receptor (DR) agonists (1 h/day, for 3 days). Intermittent METH (10 μM) exposure enhanced RyR-1 and -2 proteins and their mRNA, but not RyR-3 expression in the both types of the neurons. These METH-induced increases of RyR proteins and their mRNA were dose-dependently blocked by SCH23390 (a selective D1DR antagonist), but not a D2DR antagonist sulpiride, suggesting a regulatory role of D1DRs in RyR expression by METH in these neurons. In cerebral cortical neurons, intermittent SKF82958 (a selective D1DR agonist) exposure increased RyR-1 and -2 proteins and their mRNA, whereas quinpirole (a selective D2DR agonist) showed no effects. KT5720, a protein kinase A inhibitor, dose-dependently attenuated the METH-stimulated RyR-1 and -2 expressions in cerebral cortical neurons. METH significantly increased phosphorylation of cAMP-response element-binding protein, which was completely suppressed by SCH23390. These results indicate that RyR-1 and -2 expressions are regulated by D1DRs via the signal transduction linked to D1DRs.