Activation of phosphatidylinositol-linked novel D1 dopamine receptors inhibits high-voltage-activated Ca2+ currents in primary cultured striatal neurons.
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), alpha(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.
Ma
Li-Qun
LQ
Dept. of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd., Wuhan, Hubei 430030, China.
Liu
Chao
C
Wang
Fang
F
Xie
Na
N
Gu
Jun
J
Fu
Hui
H
Wang
Jiang-Hua
JH
Cai
Fei
F
Liu
Jue
J
Chen
Jian-Guo
JG
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000494:pharmacology; D001703:Biophysics; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D001552:Benzazepines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D010716:Phosphatidylinositols; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D013373:Substance P; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959; D006493:Heparin; D019703:Calcineurin; D010738:Type C Phospholipases; D005968:Glutamate Decarboxylase; D002118:Calcium