Mechanism of action of methylmercury on in vivo striatal dopamine release. Possible involvement of dopamine transporter.
Methylmercury (MeHg) produces significant increases in the spontaneous output of dopamine (DA) from rat striatal tissue. The mechanism through MeHg produces such increase in the extracellular DA levels could be due to increased DA release or decreased DA uptake into DA terminals. One of the aims of this study was to investigate the role of DA transporter (DAT) in the MeHg-induced DA release. Coinfusion of 400 microM MeHg and nomifensine (50 microM) or amphetamine (50 microM) produced increases in the release of DA similar to those produced by nomifensine and amphetamine alone. In the same way, MeHg-induced DA release was not attenuated under Ca(2+)-free conditions or after pretreatment with reserpine (10 mg/kg i.p.) or tetrodotoxin (TTX), suggesting that the DA release was independent of calcium and vesicular stores, as well as it was not affected by the blockade of voltage sensitive sodium channels. Thus, to investigate whether depolarization of dopaminergic terminal was able to affect MeHg-induced DA release, we infused 75 mM KCl through the dialysis membrane. Our results clearly showed a decrease induced by MeHg in the KCl-evoked DA release. Taken together, these results suggest that MeHg induces release of DA via transporter-dependent, calcium- and vesicular-independent mechanism and it decreases the KCl-evoked DA release.
Faro
L R F
LR
Departamento de Fisiologia, Centro de Ciências Biológicas, UFPA, Belém, PA, Brazil.
do Nascimento
J L M
JL
Alfonso
M
M
Durán
R
R
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000032:analysis; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D007552:Isotonic Solutions / Q000737:chemistry / Q000494:pharmacology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000502:physiology; D008767:Methylmercury Compounds / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D009627:Nomifensine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D000077331:Ringer's Solution; D013779:Tetrodotoxin / Q000494:pharmacology
D003470:Culture Media; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D007552:Isotonic Solutions; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008767:Methylmercury Compounds; D009419:Nerve Tissue Proteins; C493216:Slc6a3 protein, rat; D009627:Nomifensine; D013779:Tetrodotoxin; D000077331:Ringer's Solution; D012110:Reserpine; D000661:Amphetamine; D011188:Potassium; D002118:Calcium; D004298:Dopamine