![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 59, Issue 1, 113-121, January 2001
Department of Pharmacology and Neuroscience Program, University of
Colorado Health Sciences Center, Denver, Colorado
Presynaptic dopamine D2 receptors (D2Rs)
regulate dopamine transporter (DAT) activity in the brain. A potential
mechanism was suggested by the observations that somatodendritic
D2R activation produces hyperpolarization and the velocity
of DAT expressed in Xenopus laevis oocytes varies with
changes in membrane potential. To investigate whether D2R
regulation of DAT function is voltage-dependent, we coexpressed the
long isoform of the human (h) D2R and the hDAT in oocytes.
Most DAT substrates fully activate D2Rs at concentrations used to measure uptake. Thus, DAT function was compared under conditions of maximal D2R activation (0.1-10 µM DA) or
maximal D2R blockade (DA + 1 µM (
)-sulpiride).
D2R activation significantly increased [3H]DA
uptake into unclamped oocytes expressing relatively lower velocities.
Uptake measured with a saturating concentration of DA suggested a
D2R-induced increase in Vmax.
The D2R-mediated enhancement of DA uptake was not
associated with changes in resting membrane potential and was abolished
by pertussis toxin pretreatment. Furthermore, in voltage-clamped
oocytes, D2R activation enhanced both DA uptake and
DAT-mediated steady-state currents by as much as 70%. Activation of
D2Rs resulted in a 59% increase in cell surface binding of
the cocaine analog [3H]WIN 35,428; this effect was also
abolished by pertussis toxin pretreatment. Saturation experiments
confirmed that D2R activation was associated with an
increased Bmax and unchanged
Ki for [3H]WIN 35,428. These
results suggest that D2R-induced up-regulation of DAT
activity occurs via a voltage-independent mechanism that depends on
Gi/o activation and a rapid increase in expression of
functional DAT molecules at the cell surface.
This article has been cited by other articles:
|
|
 |
|
  Z. Xie and G. M. Miller {beta}-Phenylethylamine Alters Monoamine Transporter Function via Trace Amine-Associated Receptor 1: Implication for Modulatory Roles of Trace Amines in Brain J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 617 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zapata, B. Kivell, Y. Han, J. A. Javitch, E. A. Bolan, D. Kuraguntla, V. Jaligam, M. Oz, L. D. Jayanthi, D. J. Samuvel, et al. Regulation of Dopamine Transporter Function and Cell Surface Expression by D3 Dopamine Receptors J. Biol. Chem., December 7, 2007; 282(49): 35842 - 35854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Bolan, B. Kivell, V. Jaligam, M. Oz, L. D. Jayanthi, Y. Han, N. Sen, E. Urizar, I. Gomes, L. A. Devi, et al. D2 Receptors Regulate Dopamine Transporter Function via an Extracellular Signal-Regulated Kinases 1 and 2-Dependent and Phosphoinositide 3 Kinase-Independent Mechanism Mol. Pharmacol., May 1, 2007; 71(5): 1222 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Blakely and L. J. DeFelice All Aglow about Presynaptic Receptor Regulation of Neurotransmitter Transporters Mol. Pharmacol., May 1, 2007; 71(5): 1206 - 1208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Kahlig, B. J. Lute, Y. Wei, C. J. Loland, U. Gether, J. A. Javitch, and A. Galli Regulation of Dopamine Transporter Trafficking by Intracellular Amphetamine Mol. Pharmacol., August 1, 2006; 70(2): 542 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Kahlig, J. A. Javitch, and A. Galli Amphetamine Regulation of Dopamine Transport: COMBINED MEASUREMENTS OF TRANSPORTER CURRENTS AND TRANSPORTER IMAGING SUPPORT THE ENDOCYTOSIS OF AN ACTIVE CARRIER J. Biol. Chem., March 5, 2004; 279(10): 8966 - 8975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Moron, I. Zakharova, J. V. Ferrer, G. A. Merrill, B. Hope, E. M. Lafer, Z. C. Lin, J. B. Wang, J. A. Javitch, A. Galli, et al. Mitogen-Activated Protein Kinase Regulates Dopamine Transporter Surface Expression and Dopamine Transport Capacity J. Neurosci., September 17, 2003; 23(24): 8480 - 8488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Schmitz, C. Schmauss, and D. Sulzer Altered Dopamine Release and Uptake Kinetics in Mice Lacking D2 Receptors J. Neurosci., September 15, 2002; 22(18): 8002 - 8009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sabeti, G. A. Gerhardt, and N. R. Zahniser Acute Cocaine Differentially Alters Accumbens and Striatal Dopamine Clearance in Low and High Cocaine Locomotor Responders: Behavioral and Electrochemical Recordings in Freely Moving Rats J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 1201 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maiya, K. J. Buck, R. A. Harris, and R. D. Mayfield Ethanol-sensitive Sites on the Human Dopamine Transporter J. Biol. Chem., August 16, 2002; 277(34): 30724 - 30729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wu, M. E. A. Reith, Q. D. Walker, C. M. Kuhn, F. I. Carroll, and P. A. Garris Concurrent Autoreceptor-Mediated Control of Dopamine Release and Uptake during Neurotransmission: An In Vivo Voltammetric Study J. Neurosci., July 15, 2002; 22(14): 6272 - 6281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Prasad and S. G. Amara The Dopamine Transporter in Mesencephalic Cultures Is Refractory to Physiological Changes in Membrane Voltage J. Neurosci., October 1, 2001; 21(19): 7561 - 7567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Brown, G. R. Hanson, and A. E. Fleckenstein Cocaine-Induced Increases in Vesicular Dopamine Uptake: Role of Dopamine Receptors J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1150 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Doolen and N. R. Zahniser Protein Tyrosine Kinase Inhibitors Alter Human Dopamine Transporter Activity in Xenopus Oocytes J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 931 - 938. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
