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Titolo:
Inhibitors of Na+/H+ and Na+/Ca2+ exchange potentiate methamphetamine-induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity
Autore:
Callahan, BT; Cord, BJ; Yuan, J; McCann, UD; Ricaurte, GA;
Indirizzi:
Johns Hopkins Med Inst, Dept Neurol & Psychiat, Baltimore, MD 21224 USA Johns Hopkins Med Inst Baltimore MD USA 21224 at, Baltimore, MD 21224 USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 77, anno: 2001,
pagine: 1348 - 1361
SICI:
0022-3042(200106)77:5<1348:IONANE>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
STRIATAL DOPAMINE; MICE LACKING; RAT STRIATUM; NA+,K+-ATPASE ACTIVITY; TERMINAL DEGENERATION; ENERGY-METABOLISM; AMILORIDE ANALOGS; INDUCED DEPLETION; BODY-TEMPERATURE; OXIDATIVE STRESS;
Keywords:
amiloride; amphetamines; dopamine; Na+/H+ and Na+/Ca2+ exchangers; transporters;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
82
Recensione:
Indirizzi per estratti:
Indirizzo: Ricaurte, GA Johns Hopkins Med Inst, Dept Neurol, 5501 Hopkins Bayview Circle,Rm 5B71E,Baltimore, MD 21224 USA Johns Hopkins Med Inst 5501 Hopkins Bayview Circle,Rm 5B71E Baltimore MD USA 21224
Citazione:
B.T. Callahan et al., "Inhibitors of Na+/H+ and Na+/Ca2+ exchange potentiate methamphetamine-induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity", J NEUROCHEM, 77(5), 2001, pp. 1348-1361

Abstract

Although the neurotoxic potential of methamphetamine (METH) is well established, underlying mechanisms have yet to be identified. In the present study, we sought to determine whether ionic dysregulation was a feature of METHneurotoxicity. In particular, we reasoned that if METH impairs the function of Na+/H+ and/or Na+/Ca2+ antiporters by compromising the inward Na+ gradient [via prolonged DA transporter (DAT) activation and Na+/K+ ATPase inhibition], then amiloride (AMIL) and other inhibitors of Na+/H+ and/or Na+/Ca2 exchange would potentiate METH neurotoxicity. To test this hypothesis, mice were treated with METH alone or in combination with AMIL or one of its analogs; 1 week later, the animals were killed for studies of dopamine (DA) neuronal integrity. AMIL markedly potentiated the toxic effect of METH on DA neurons. Potentiation was not caused by increased core temperature, enhanced DAT activity or higher METH brain levels. The DAT inhibitor, WIN-35,428, protected completely against METH-induced DA neurotoxicity in AMIL pretreated animals, suggesting that the potentiating effects of AMIL require a METH/DAT interaction. Findings with METH and AMIL were extended to six other AMIL analogs (MIA, EIPA, DIMA, BENZ, BEP, DiCBNZ), another species (rats), and neuronal type (5-HT neurons). These results support the notion that ionic dysregulation may play a role in METH neurotoxicity.

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Documento generato il 23/01/20 alle ore 03:24:28