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Titolo:
Transport pathways for therapeutic concentrations of lithium in rat liver
Autore:
Shahabi, V; van Rossum, GDV;
Indirizzi:
Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA Temple Univ Philadelphia PA USA 19140 armacol, Philadelphia, PA 19140 USA
Titolo Testata:
JOURNAL OF MEMBRANE BIOLOGY
fascicolo: 2, volume: 172, anno: 1999,
pagine: 101 - 111
SICI:
0022-2631(19991115)172:2<101:TPFTCO>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
NA+-H+ EXCHANGER; RED-BLOOD-CELLS; LI+ COUNTERTRANSPORT SYSTEM; SODIUM-PROTON EXCHANGE; ESSENTIAL-HYPERTENSION; HUMAN-ERYTHROCYTES; MEMBRANE-VESICLES; POTASSIUM; VOLUME; AMILORIDE;
Keywords:
lithium therapeutic concentrations; transport kinetics; hepatocytes; amiloride; phloretin; Li/Na exchange; Na/H exchange;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: van Rossum, GDV Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA Temple Univ Philadelphia PA USA 19140 lphia, PA 19140 USA
Citazione:
V. Shahabi e G.D.V. van Rossum, "Transport pathways for therapeutic concentrations of lithium in rat liver", J MEMBR BIO, 172(2), 1999, pp. 101-111

Abstract

Although both amiloride- and phloretin-sensitive Na+/Li+ exchange activities have been reported in mammalian red blood cells, it is still unclear whether or not the two are mediated by the same pathway. Also, little is knownabout the relative contribution of these transport mechanisms to the entryof therapeutic concentrations of Li+ (0.2-2 mM) into cells other than erythrocytes. Here, we describe characteristics of these transport systems in rat isolated hepatocytes in suspension. Uptake of Li+ by hepatocytes, preloaded with Na+ and incubated in the presence of ouabain and bumetanide, comprised three components. (a) An amiloride-sensitive component, with apparent K-m, 1.2 mM Li+, V-max 40 mu mol.(kg dry wt.min)(-1), showed increased activity at low intracellular pH. The relationship of this component to the concentration of intracellular H+ was curvilinear suggesting a modifier role of [H+](i). This system persisted in Na+-depleted cells, although with apparent K-m 3.8 mM. (b) A phloretin-sensitive component. with K-m 1.2 mM, V-max21 mu mol.(kg.min)(-1), was unaffected by pH but was inactive in Na+-depleted cells. Phloretin inhibited Li+ uptake and Na+ efflux in parallel. (c) Aresidual uptake increased linearly with the external Li+ concentration andrepresented an increasing proportion of the total uptake. The results strongly suggest that the amiloride-sensitive and the phloretin-sensitive Li+ uptake in rat liver are mediated by two separate pathways which can be distinguished by their sensitivity to inhibitors and intracellular [H+].

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Documento generato il 17/01/21 alle ore 18:16:46