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Titolo:
A lithium-induced conformational change in serotonin transporter alters cocaine binding, ion conductance, and reactivity of Cds-109
Autore:
Ni, YG; Chen, JG; Androutsellis-Theotokis, A; Huang, CJ; Moczydlowski, E; Rudnick, G;
Indirizzi:
Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA Yale Univ NewHaven CT USA 06510 Dept Pharmacol, New Haven, CT 06510 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 33, volume: 276, anno: 2001,
pagine: 30942 - 30947
SICI:
0021-9258(20010817)276:33<30942:ALCCIS>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN DOPAMINE TRANSPORTER; CLONING; NOREPINEPHRINE; ACCESSIBILITY; EXPRESSION; PERMEATION; SUBSTRATE; RESIDUES; CYSTEINE; CHANNEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Rudnick, G Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT06510 USA Yale Univ 333 Cedar St New Haven CT USA 06510 ven, CT 06510 USA
Citazione:
Y.G. Ni et al., "A lithium-induced conformational change in serotonin transporter alters cocaine binding, ion conductance, and reactivity of Cds-109", J BIOL CHEM, 276(33), 2001, pp. 30942-30947

Abstract

Inactivation of serotonin transporter (SERT) expressed in HeLa cells by [2-(trimethylammonium)ethyl]-methanethiosulfonate (MTSET) occurred much more readily when Na+ in the reaction medium was replaced with Li+. This did notresult from a protective effect of Na+ but rather from a Li+-specific increase in the reactivity of Cys-109 in the first external loop of the transporter. Li+ alone of the alkali cations caused this increase in reactivity. Replacing Na+ with N-methyl-D-glucamine (NMDG(+)) did not reduce the affinity of cocaine for SERT, as measured by displacement of a high affinity cocaine analog, but replacement of Na+ with Li+ led to a 2-fold increase in the KD for cocaine. The addition of either cocaine or serotonin (5-HT) protected SERT against MTSET inactivation. When SERT was expressed in Xenopus oocytes, inward currents were elicited by superfusing the cell with 5-HT (in thepresence of Na+) or by replacing Na+ with Li+ but not NMDG(+). MTSET treatment of oocytes in Li+ but not in Na+ decreased both 5-HT and Li+ induced currents, although 5-HT-induced currents were inhibited to a greater extent. Na+ antagonized the effects of Li+ on both inactivation and current. Theseresults are consistent with Li+ inducing a conformational change that exposes Cys-109, decreases cocaine affinity, and increases the uncoupled inwardcurrent.

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Documento generato il 12/07/20 alle ore 12:04:22