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J Neurophysiol 101: 2230-2238, 2009. First published February 18, 2009; doi:10.1152/jn.90345.2008
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RESEARCH-ARTICLE

Activation of Phosphatidylinositol-Linked Novel D1 Dopamine Receptors Inhibits High-Voltage-Activated Ca2+ Currents in Primary Cultured Striatal Neurons

Li-Qun Ma1,*, Chao Liu13,*, Fang Wang13, Na Xie1, Jun Gu1, Hui Fu13, Jiang-Hua Wang1, Fei Cai1, Jue Liu1 and Jian-Guo Chen13

1Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; 2Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan; and 3Hubei Key Laboratory of Neurological Diseases (HUST), Wuhan, China

Submitted 9 March 2008; accepted in final form 9 February 2009

ABSTRACT

Recent evidences indicate the existence of a putative novel phosphatidylinositol (PI)-linked D1 dopamine receptor that 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 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (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, {alpha}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.

Present address and address for reprint requests and other correspondence: J.-G. Chen, Dept. of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan, Hubei 430030, China (E-mail Chenj{at}mails.tjmu.edu.cn).






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