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Titolo:
Ion dependence of carrier-mediated release in dopamine or norepinephrine transporter-transfected cells questions the hypothesis of facilitated exchange diffusion
Autore:
Pifl, C; Singer, EA;
Indirizzi:
Univ Vienna, Inst Biochem Pharmacol, A-1090 Vienna, Austria Univ Vienna Vienna Austria A-1090 chem Pharmacol, A-1090 Vienna, Austria Univ Vienna, Inst Pharmacol, A-1090 Vienna, Austria Univ Vienna Vienna Austria A-1090 Inst Pharmacol, A-1090 Vienna, Austria
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 5, volume: 56, anno: 1999,
pagine: 1047 - 1054
SICI:
0026-895X(199911)56:5<1047:IDOCRI>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
CATECHOLAMINE TRANSPORTERS; CORPUS STRIATUM; AMPHETAMINE; EFFLUX; NORADRENALINE; MECHANISM; COCAINE; SODIUM; SYNAPTOSOMES; INDUCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Pifl, C Univ Vienna, Inst Biochem Pharmacol, Borschkogasse 8A, A-1090 Vienna, Austria Univ Vienna Borschkogasse 8A Vienna Austria A-1090 ienna, Austria
Citazione:
C. Pifl e E.A. Singer, "Ion dependence of carrier-mediated release in dopamine or norepinephrine transporter-transfected cells questions the hypothesis of facilitated exchange diffusion", MOLEC PHARM, 56(5), 1999, pp. 1047-1054

Abstract

The mechanism of release mediated by the human dopamine and norepinephrinetransporter (DAT and NET, respectively) was studied by a superfusion technique in human embryonic kidney 293 cells stably transfected with the respective transporter cDNA and loaded with the metabolically inert substrate [H-3]1-methyl-4-phenylpyridinium. Release was induced by amphetamine, dopamine, and norepinephrine or by lowering the sodium or chloride concentration inthe superfusion buffer (isoosmotic replacement by lithium and isethionate,respectively). Efflux of [H-3]1-methyl-4-phenylpyridinium was analyzed at 30-s time resolution. In both transporters, release induced by the substrates amphetamine, dopamine, and norepinephrine followed the same time course as release induced by the removal of chloride and was faster than that caused by the removal of sodium. In the presence of low sodium (DAT: 10 mM; NET: 5 mM) none of the substrates was able to induce release from either type of cell, but adding back sodium to control conditions promptly restored thereleasing action. In the presence of low chloride (DAT: 3 mM; NET: 2 mM), however, amphetamine as well as the catecholamines stimulated release from both types of cell. In contrast with the ion dependence of release observedin superfusion experiments, uptake initial rates of substrates at concentrations used in release experiments were the same or even higher at low sodium than at low chloride. The results indicate a decisive role of extracellular sodium for carrier-mediated release unrelated to the sodium-dependent uptake of the releasing substrate, and suggest a release mechanism differentfrom simple exchange diffusion considering only the amines as substrates.

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Documento generato il 04/04/20 alle ore 15:19:54