Submitted on March 9, 2008
Revised on February 9, 2009
Accepted on February 9, 2009
Activation of phosphatidylinositol-linked novel D1 dopamine receptors inhibits high voltage activated Ca2+ currents in primary cultured striatal neurons
Li-Qun Ma, Fang Wang, Chao Liu, Na Xie, Jun Gu, Hui Fu, Jiang-Hua Wang, Fei Cai, Jue Liu, and Jian-Guo Chen1*
1 Tongji Medical College, University of Science and Technology
* To whom correspondence should be addressed. E-mail: chenj{at}mails.tjmu.edu.cn.
Recent evidences indicate the existence of a putative novel phosphatidylinositol (PI) -linked D1 dopamine receptor, which mediates excellent anti-Parkinsonian but less severe dyskinesia action. To further understand the basic physiological function of this receptor in brain, the effects of a PI-linked D1 dopamine receptor selective agonist SKF83959 on high voltage activated (HVA) Ca2+ currents in primary cultured striatal neurons were investigated by whole-cell patch-clamp technique. The results indicated that stimulation by SKF83959 induced an inhibition of HVA Ca2+ currents in a dose-dependent manner in substance-P (SP)-immunoreactive striatal neurons. Application of D1 receptor, but not D2, 
1 adrenergic, 5-HT receptor or cholinoceptor antagonist prevented SKF83959-induced reduction, indicating that a D1 receptor-mediated event, assumed via PI-linked D1 receptor. SKF83959-induced inhibitory modulation was mediated by activation of phospholipase C (PLC), mobilization of intracellular Ca2+ stores and activation of calcineurin. Furthermore, the inhibitory effects were attenuated significantly by the L-type calcium channel antagonist nifedipine, suggesting that L-type calcium channels involved in the regulation induced by SKF83959. These findings may help to further understand the functional role of the PI-linked dopamine receptor in brain.
