Bidirectional regulation of Ca2+/calmodulin-dependent protein kinase II activity by dopamine D4 receptors in prefrontal cortex

Molecular Pharmacology
Zhenglin Gu, Zhen Yan

Abstract

The dopamine D4 receptor in prefrontal cortex (PFC) plays a key role in normal mental functions and neuropsychiatric disorders. However, the cellular mechanisms and physiological actions of D4 receptors remain elusive. In this study, we found that activation of D4 receptors in PFC exerts a complex regulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII), a multifunctional enzyme critically involved in synaptic plasticity that is fundamental for cognitive and emotional processes. In PFC slices with high neuronal activity, application of the D4 receptor agonist [4-phenylpiperazinyl)-methyl]benzamide (PD168077) produced a potent reduction of the CaMKII activity, whereas in PFC slices with low neuronal activity, PD168077 caused a marked increase of the CaMKII activity. The D4 up-regulation of CaMKII activity was through the stimulation of phospholipase C pathway and elevation of intracellular Ca2+ via ionsitol-1,4,5-triphosphate receptors. These results reveal a bidirectional regulation of CaMKII activity by PFC D4 receptors in response to changes in neuronal activity, and a nonclassic signaling pathway underlying the D4 up-regulation of CaMKII activity. This modulation provides a unique and flexible mechanism for D4 rece...Continue Reading

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Citations

Jan 21, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Simona PerraHitoshi Morikawa
Dec 8, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eunice Y YuenZhen Yan
Jan 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eunice Y Yuen, Zhen Yan
Jun 8, 2014·Current Opinion in Neurobiology·Farzan Nadim, Dirk Bucher
Dec 18, 2015·Trends in Pharmacological Sciences·Christian P MüllerK Peter Giese
Jul 21, 2005·The European Journal of Neuroscience·Abigail M BrownRoger J Colbran
Apr 22, 2017·Current Opinion in Neurobiology·Friedemann ZenkeSurya Ganguli
Apr 24, 2016·Journal of the American Heart Association·Ye ZhangWeibin Shi
Jan 4, 2008·American Journal of Physiology. Endocrinology and Metabolism·Hong-Wei ChangBor-Shen Hsieh
Jul 26, 2013·The Journal of Biological Chemistry·Eunice Y YuenZhen Yan

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