Dopamine release evoked by beta scorpion toxin, tityus gamma, in prefrontal cortical slices is mediated by intracellular calcium stores.
1. We have investigated the effect of tityus gamma (TiTX gamma) scorpion toxin on the release of [3H]dopamine in rat brain prefrontal cortical slices. The stimulatory effect of TiTX gamma on the release of [3H]dopamine was dose/time-dependent with an EC50 of 0.01 microM. 2. Tetrodotoxin blocked the TiTX gamma-induced release of [3H]dopamine, indicating the dependency for Na+ channels. 3. EGTA had no effect on the TiTX gamma-induced release of [3H]dopamine, indicating the process is independent of extracellular calcium. Release of [3H]dopamine evoked by TiTX gamma was inhibited by 57% by BAPTA, a chelator of intracellular calcium. 4. Xestospongin and 2-APB, putative blockers of IP3-sensitive release of intracellular calcium stores, caused an equal and significant inhibition of 24% of the TiTX gamma-induced release of [3H]dopamine, while the slight inhibition evoked by dantrolene, a putative blocker of ryanodine-sensitive calcium store was not significant. 5. Nomifensine and ascorbic acid, blockers of dopamine transporter (DAT), caused an inhibition of 27 and 29%, respectively, on the toxin-induced release of [3H]dopamine suggesting that most of the TiTX gamma-induced release of dopamine is not due to the reversal of Na+ gradient. 6. In conclusion the majority of the TiTX gamma-induced release of [3H]dopamine is exocytotic and mobilizes calcium from the intracellular IP3-sensitive calcium stores.
Fernandes
Virginia Maria Vidigal
VM
Departamento de Farmacologia, Instituto de Ciências Biológicas, UFMG, 31270-901-Belo Horizonte, MG-Brasil.
Romano-Silva
Marco Aurélio
MA
Gomes
Dawidson Assis
DA
Prado
Marco Antonio Máximo
MA
Santos
Tasso Moraes
TM
Gomez
Marcus Vinicius
MV
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000494:pharmacology*
D009498:Neurotoxins; D012604:Scorpion Venoms; C119038:Ts-gamma neurotoxin; D004298:Dopamine