Involvement of noradrenaline transporters in S-nitrosocysteine-stimulated noradrenaline release from rat brain slices: existence of functional Na(+)-independent transporter activity.
Noradrenaline (NA) can be released by both exocytosis and by the membrane transporter responsible for transmitter uptake. Previously, we reported that S-nitrosocysteine (SNC), an S-nitrosothiol, stimulated [3H]NA release from the rat hippocampus. In this study, we investigated the involvement of the NA transport system in SNC-stimulated NA release from rat brain (cerebral cortex and hippocampus) slices. [3H]NA release by SNC in normal Na(+) (148 mM)-containing buffer from both slices was slightly, but significantly, inhibited by 1 microM desipramine, an NA transporter inhibitor. [3H]NA release in low Na(+) (under 14 mM)-containing buffer was inhibited by over 50% by desipramine. [3H]NA release by tyramine from both slices in normal and low Na(+) buffer was almost completely inhibited by desipramine. [3H]NA uptake into cerebral cortical slices was observed in low Na(+) buffer at 20-30% of normal Na(+) buffer levels. [3H]NA uptake in both normal and low Na(+) buffers was inhibited by desipramine and by SNC. Although [3H]NA uptake in normal Na(+) buffer was almost completely inhibited by 500 microM ouabain, the uptake in low Na(+) buffer was resistant to ouabain. These findings suggest the existence of a functional Na(+)-independent NA transport system and that SNC stimulates NA release at least partially via this system in brain slices.
Maekawa
M
M
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, 060-0812, Sapporo, Japan.
Murayama
T
T
Nomura
Y
Y
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000145:classification / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009603:Nitroso Compounds / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism* / Q000493:pharmacokinetics; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D026403:S-Nitrosothiols; D012964:Sodium / Q000378:metabolism*; D027981:Symporters; D013876:Thiophenes / Q000494:pharmacology; D014316:Tritium
D018759:Adrenergic Uptake Inhibitors; D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D004048:Diethylamines; D009603:Nitroso Compounds; D050484:Norepinephrine Plasma Membrane Transport Proteins; D026403:S-Nitrosothiols; C493226:Slc6a2 protein, rat; D027981:Symporters; D013876:Thiophenes; D014316:Tritium; C082372:T 588; D010042:Ouabain; D011189:Potassium Chloride; D000584:Amiloride; D012110:Reserpine; C021315:S-nitrosocysteine; D012964:Sodium; D003545:Cysteine; D003891:Desipramine; D009638:Norepinephrine