Abstract Recent evidences indicate the existence of a putative novel phosphatidylinositol (PI)-linked D 1 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 D 1 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) Ca 2+ 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 Ca 2+ currents in a dose-dependent manner in substance-P (SP)-immunoreactive striatal neurons. Application of D 1 receptor, but not D 2 , α 1 adrenergic, 5-HT receptor, or cholinoceptor antagonist prevented SKF83959-induced reduction, indicating that a D 1 receptor-mediated event assumed via PI-linked D 1 receptor. SKF83959-induced inhibitory modulation was mediated by activation of phospholipase C (PLC), mobilization of intracellular Ca 2+ 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. Footnotes ↵ * L.-Q. Ma and C. Liu contributed equally to this work. Copyright © 2009 the American Physiological Society
Journal of Neurophysiology – The American Physiological Society
Published: May 1, 2009
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