| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 33, 30942-30947, August 17, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Pharmacology, Yale University School of
Medicine, New Haven, Connecticut 06520
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 not result 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 the presence 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. These results are
consistent with Li+ inducing a conformational change that
exposes Cys-109, decreases cocaine affinity, and increases the
uncoupled inward current.
A Lithium-induced Conformational Change in Serotonin Transporter
Alters Cocaine Binding, Ion Conductance, and Reactivity of Cys-109*
,
*
This work was supported by grants from the National
Institute on Drug Abuse at the National Institutes of Health.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Dept. of Physiology, University of Texas
Southwestern Medical Center, Dallas, TX 75390.
§
Present address: Dept. of Pharmacology, Albert Einstein College of
Medicine, Bronx, NY 10461.
¶
Present address: Physiome Sciences, Inc., Princeton, NJ
08540-6604.
To whom correspondence should be addressed: Dept. of
Pharmacology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510. Tel.: 203-785-4548; Fax: 203-737-2027; E-mail: gary.rudnick@yale.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y.-W. Zhang and G. Rudnick The Cytoplasmic Substrate Permeation Pathway of Serotonin Transporter J. Biol. Chem., November 24, 2006; 281(47): 36213 - 36220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhou, E. Zomot, and B. I. Kanner Identification of a Lithium Interaction Site in the {gamma}-Aminobutyric Acid (GABA) Transporter GAT-1 J. Biol. Chem., August 4, 2006; 281(31): 22092 - 22099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sato, Y.-W. Zhang, A. Androutsellis-Theotokis, and G. Rudnick Analysis of Transmembrane Domain 2 of Rat Serotonin Transporter by Cysteine Scanning Mutagenesis J. Biol. Chem., May 28, 2004; 279(22): 22926 - 22933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Adams and L. J. DeFelice Ionic Currents in the Human Serotonin Transporter Reveal Inconsistencies in the Alternating Access Hypothesis Biophys. J., September 1, 2003; 85(3): 1548 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Androutsellis-Theotokis, N. R. Goldberg, K. Ueda, T. Beppu, M. L. Beckman, S. Das, J. A. Javitch, and G. Rudnick Characterization of a Functional Bacterial Homologue of Sodium-dependent Neurotransmitter Transporters J. Biol. Chem., April 4, 2003; 278(15): 12703 - 12709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Androutsellis-Theotokis and G. Rudnick Accessibility and Conformational Coupling in Serotonin Transporter Predicted Internal Domains J. Neurosci., October 1, 2002; 22(19): 8370 - 8378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Li and H. A. Lester Early Fluorescence Signals Detect Transitions at Mammalian Serotonin Transporters Biophys. J., July 1, 2002; 83(1): 206 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S. Ramsey and L. J. DeFelice Serotonin Transporter Function and Pharmacology Are Sensitive to Expression Level. EVIDENCE FOR AN ENDOGENOUS REGULATORY FACTOR J. Biol. Chem., April 19, 2002; 277(17): 14475 - 14482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lopez-Corcuera, E. Nunez, R. Martinez-Maza, A. Geerlings, and C. Aragon Substrate-induced Conformational Changes of Extracellular Loop 1 in the Glycine Transporter GLYT2 J. Biol. Chem., November 9, 2001; 276(46): 43463 - 43470. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
