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Regulation of Bcl-2 Protein Expression in Human Neuroblastoma SH-SY5Y Cells: Positive and Negative Effects of Protein Kinases C and A, Respectively
Authors:Yasuhiro Itano,Akihiro Ito,Takashi Uehara, &dagger   Yasuyuki Nomura
Affiliation:Department of Pharmacology, Glaxo Institute of Applied Pharmacology, Cambridge University, Cambridge, England
Abstract:Abstract: Nitric oxide (NO), liberated from the photoactive donor Roussin's black salt (RBS), was investigated for its ability to release tritium from [3H]dopamine-loaded rat striatal slices. Our results show that illumination of RBS-pretreated striatal slices caused an increase in basal dopamine release, which was reduced by ∼73% in the presence of oxyhaemoglobin (10 µ M ), indicating that it was mediated by liberation of NO. The release was insensitive to removal of extracellular calcium yet was not due to gross cellular damage of the tissue, as there was no detectable increase in lactate dehydrogenase release. Chelation of intracellular calcium with 1,2-bis( o -aminophenoxy)ethane- N,N,N',N' -tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM; 10 µ M ) had no effect on the dopamine release stimulated by illumination of RBS-pretreated slices. The concentration of BAPTA-AM was adequate to chelate intracellular calcium because it inhibited release evoked by the calcium ionophore ionomycin (10 µ M ). Superfusion with zaprinast (10 µ M ) had no effect on RBS-induced dopamine release, suggesting that a mechanism independent of cyclic GMP is involved. This study indicates that NO has a stimulatory effect on striatal dopamine release in vitro that is independent of calcium.
Keywords:Nitric oxide    Dopamine    Striatum    Calcium-independent release    Neurotransmitter release    Roussin's black salt
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