Effect of nitric oxide donors on endogenous dopamine release from rat striatal slices. II: The role of voltage-dependent sodium channels, calcium channel activation, reverse transport mechanism, guanylate cyclase and endogenous glutamate.
Incubation of striatal slices with sodium nitroprusside (SNP) or hydroxylamine (HA) for 60 min caused a dose-dependent increase in dopamine (DA) release. This effect was inhibited completely by tetrodotoxin (TTX) (1 microM) if low concentrations of SNP (1 microM) or HA (10 and 100 microM) were tested. Although-higher concentration of SNP (10 and 100 microM) and HA (500 microM) were still effective in stimulating DA release, increases observed under these conditions were less than the values found in the absence of TTX. Verapamil (10 microM), but not omega-conotoxin (100 nM), significantly reduced DA release stimulated by high concentrations of SNP or HA. When verapamil was combined with TTX, moreover, SNP and HA failed to stimulate DA release. If striatal slices were incubated in the presence of nomifensine (10 microM), SNP and HA did not enhance DA release. SNP and HA-induced depletions in tissue DA levels were also protected by nomifensine. Inhibition of guanylate cyclase with 10 microM of methylene blue could not reduce the effects of NO-donors. SNP and HA also failed to alter endogenous glutamate release from striatal slices. Similarly, SNP and HA-induced increases in DA release were not affected by kynurenic acid and MK-801. These results indicate that NO-donors SNP and HA stimulate DA release by facilitating reverse DA transport. This effect seems to be dependent on the activation of both voltage dependent sodium channels and L-type of calcium channels. Results presented here also indicate that neither endogenous glutamate nor guanylate cyclase activation plays an intermediary role in stimulatory effects of NO-donors on DA release from rat striatal slices.
Büyükuysal
R L
RL
Uludağ University, Medical School, Department of Pharmacology, Bursa, Turkey.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D019811:Hydroxylamine / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000378:metabolism / Q000494:pharmacology*; D009627:Nomifensine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D010455:Peptides; D015222:Sodium Channels; D014665:Vasodilator Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D009599:Nitroprusside; D009627:Nomifensine; D019811:Hydroxylamine; D009569:Nitric Oxide; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D020866:omega-Conotoxin GVIA; D014700:Verapamil; D006162:Guanylate Cyclase; D007736:Kynurenic Acid; D008751:Methylene Blue; D004298:Dopamine