Trimethyltin and triethyltin differentially induce spontaneous noradrenaline release from rat hippocampal slices.
The environmental contaminants trimethyltin (TMT) and triethyltin (TET) stimulated the spontaneous release of [(3)H]noradrenaline ([(3)H]NA) from hippocampal slices in a time- and concentration-dependent manner. TMT was the most potent compound, exhibiting an EC50 value 10-fold lower (3.8 microM) than that of TET (39.5 microM). Metal-evoked [(3)H]NA release did not increase in the absence of desipramine and was completely blocked by reserpine preincubation, indicating a vesicular origin of [(3)H]NA release but not a mechanism involving reversal of the transmitter transporter. The voltage-gated Na(+) channel blocker tetrodotoxin (TTX) did not affect metal-evoked [(3)H]NA release. [(3)H]NA release elicited by TMT was partially extracellular Ca(2+)-dependent, since it was significantly decreased in a Ca(2+)-free EGTA-containing medium, whereas TET induced an extracellular Ca(2+)-independent release of [(3)H]NA. Neither inhibitors of Ca(2+)-entry through Na(+)/Ca(2+)exchanger and voltage-gated calcium channels, nor agents that interfere with Ca(2+)-mobilization from intracellular stores affected [(3)H]NA release induced by TMT. TET-evoked [(3)H]NA release was reduced by ruthenium red, which depletes mitochondrial Ca(2+)stores, but was not modified by caffeine and thapsigargin, which interfere with Ca(2+)mobilization from endoplasmic reticulum. The fact that TET effect was also attenuated by DIDS, an inhibitor of anion exchange, indicates that the effect of TET on spontaneous [(3)H]NA release may be mediated by intracellular mobilization of Ca(2+) from mitochondrial stores through a Cl(-) dependent mechanism.
Gassó
S
S
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona, CSIC, IDIBAPS, Spain.
Sanfeliu
C
C
Suñol
C
C
Rodríguez-Farré
E
E
Cristòfol
R M
RM
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004785:Environmental Pollutants / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007477:Ions; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014267:Triethyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*; D014316:Tritium; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D002712:Chlorides; D004785:Environmental Pollutants; D007477:Ions; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D014267:Triethyltin Compounds; D014298:Trimethyltin Compounds; D014316:Tritium; C046488:trimethyltin; D013779:Tetrodotoxin; D004533:Egtazic Acid; C031575:triethyltin; D020866:omega-Conotoxin GVIA; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine