Dopamine-regulated phosphorylation of synaptic vesicle-associated proteins in rat neostriatum and substantia nigra.
Dopamine, acting through dopamine D1 receptors and cyclic AMP-dependent protein kinase, has been found to increase the state of phosphorylation of the synaptic vesicle-associated phosphoproteins synapsin I and protein III in slices of rat neostriatum and substantia nigra. In the neostriatum, the effect of dopamine was mimicked by SKF 38393, a D2 receptor agonist, and was abolished by preincubation of the slices with fluphenazine or SCH 23390, antipsychotic drugs which are potent D1 receptor antagonists, but not by the D2 receptor antagonists l-sulpiride or spiroperidol. The maximal effect of dopamine in the neostriatum represented approximately 30-35% of the maximal effect induced by 8-bromo cyclic AMP, suggesting that a similar fraction of nerve terminals in the neostriatum may express the dopamine D1 receptor. Evidence for a small population of beta-adrenergic receptors regulating nerve terminal protein phosphorylation in the neostriatum, distinct from the D1 dopamine receptors, was also obtained. In the substantia nigra, the effect of dopamine also appeared to be mediated through a D1 dopamine receptor, since it was abolished by fluphenazine and SCH 23390. The maximal effect of dopamine in the substantia nigra represented approximately two-thirds of the effect induced by 8-bromo cyclic AMP, suggesting that a similar fraction of nerve terminals in the substantia nigra may express the dopamine D1 receptor. The ability of dopamine D1 receptor activation to stimulate both synapsin I and protein III phosphorylation and GABA release in both the neostriatum and substantia nigra may be causally linked.
Walaas
S I
SI
Laboratory of Molecular and Cellular Neurosciences, Rockefeller University, New York, NY 10021.
Sedvall
G
G
Greengard
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P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D016704:Synapsins; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D001552:Benzazepines; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016704:Synapsins; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine