Evidence that nitric oxide causes calcium-independent release of [3H] dopamine from rat striatum in vitro.
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 approximately 73% in the presence of oxyhaemoglobin (10 microM), 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-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester (BAPTA-AM; 10 microM) 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 microM). Superfusion with zaprinast (10 microM) 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.
Department of Pharmacology, Glaxo Institute of Applied Pharmacology, Cambridge University, England.
T L
TL
Stewart
A D
AD
Michel
M D
MD
Black
P P
PP
Humphrey
D000818:Animals; D002118:Calcium; D002614:Chelating Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000528:radiation effects; D058085:Iron Compounds; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds; D010782:Photolysis; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D002614:Chelating Agents; D006454:Hemoglobins; D007502:Iron Chelating Agents; D058085:Iron Compounds; D009603:Nitroso Compounds; D011688:Purinones; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D009569:Nitric Oxide; C078952:Roussin's Black Salt; D004533:Egtazic Acid; D015759:Ionomycin; C011145:zaprinast; D002118:Calcium; D004298:Dopamine