- 作者: Rong Chen Jianning Wei Stephen C. Fowler Jang-Yen Wu
- 作者服務機構: Department of Pharmacology and Toxicology and Molecular Biosciences, University of Kansas, Lawrence, Kans.; Department of Biomedical Science, Florid Atlantic University, Boca Raton, Fla., USA
- 中文摘要: --
- 英文摘要: We have previously shown that the membrane-associat-ed form of the GABA-synthesizing enzyme, glutamatedecarboxylase 65(GAD65),is activated by synaptic vesi-cle proton gradient-mediated protein phosphorylation.We now report that the rate-limiting enzyme in dopa-mine(DA) biosynthesis, tyrosine hydroxylase (TH),isregulated similarly to GAD65. The membrane-associatedform of TH(MTH)was activated by conditions favoringprotein phosphorylation (e.g.ATP) and was inhibited byphosphatase(e.g.calf intestine phosphatase).Further-more,the ATP-mediated activation of MTH was abol-ished by conditions that disrupted the proton gradient ofsynaptic vesicles, e.g.the presence of carbonyl cyanidem-chorophenylhydrazone, gramicidin,or the V-typeATPase inhibitor (bafilomycin),but not the P-typeATPase inhibitor (vanadate).Moreover, DA newly syn-thesized from tyrosine by MTH and membrane-associat-ed aromatic amino acid decarboxylase was taken uppreferentially rather than pre-existing DA. Therefore, thepreviously proposed model showing close coupling be-tween GABA synthesis and GABA packaging into synap-tic vesicles by vesicular GABA transporters is also appli-cable to the DA system.Hence, it is concluded that thereis a general coupling mechanism between neurotrans-mitter synthesis and packaging of transmitter into synap-tic vesicles.
- 中文關鍵字: --
- 英文關鍵字: Dopamine synthesis. Membrane-Associated tyrosine hydroxylase. Synaptic vesicles. Protein phosphorylation. Dopamine packaging