![[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}
|
|
|
|
|
||
SC Wall, RB Innis and G Rudnick
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
The iodinated cocaine analog 2 beta-carbomethoxy-3 beta-(4- [125I]iodophenyl)tropane (beta-[125I]CIT) binds with high affinity to the platelet plasma membrane serotonin transporter, as previously reported for dopamine transporters from rat brain [Eur. J. Pharmacol. 194:133-134 (1991)]. Unlabeled beta-CIT also inhibits serotonin transport by platelet membrane vesicles. In both rat striatal membranes and platelet plasma membranes, beta-[125I]CIT binding was found to be pH dependent, with a pKa of 6.4-6.9, and did not require the presence of Cl-. Na+ dramatically stimulated beta-[125I]CIT binding to both serotonin and dopamine transporters, although a small fraction of beta- [125I]CIT binding to the serotonin transporter was observed in the absence of Na+. The substrates serotonin and dopamine competed with beta-[125I]CIT for binding to their respective transporters. However, substrate affinity was enhanced by Cl-, whereas beta-[125I]CIT binding affinity was not. [3H]Imipramine binding to the platelet serotonin transporter and [3H]GBR-12935 binding to the dopamine transporter were not inhibited by decreasing the pH from 8 to 6.5. Likewise, the ability of serotonin to compete with [3H]imipramine binding and that of dopamine to inhibit [3H]GBR-12935 binding were equal at pH 6.5 or 8. Thus, beta-[125I]CIT binding to biogenic amine transporters is distinct from serotonin or dopamine binding by virtue of its inhibition by H+ and its insensitivity to Cl-.
This article has been cited by other articles:
|
|
 |
|
  M. T. Jacobs, Y.-W. Zhang, S. D. Campbell, and G. Rudnick Ibogaine, a Noncompetitive Inhibitor of Serotonin Transport, Acts by Stabilizing the Cytoplasm-facing State of the Transporter J. Biol. Chem., October 5, 2007; 282(40): 29441 - 29447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
V. M. Korkhov, M. Holy, M. Freissmuth, and H. H. Sitte The Conserved Glutamate (Glu136) in Transmembrane Domain 2 of the Serotonin Transporter Is Required for the Conformational Switch in the Transport Cycle J. Biol. Chem., May 12, 2006; 281(19): 13439 - 13448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Zhang and G. Rudnick Cysteine-scanning Mutagenesis of Serotonin Transporter Intracellular Loop 2 Suggests an {alpha}-Helical Conformation J. Biol. Chem., September 2, 2005; 280(35): 30807 - 30813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Magnani, C. G. Tate, S. Wynne, C. Williams, and J. Haase Partitioning of the Serotonin Transporter into Lipid Microdomains Modulates Transport of Serotonin J. Biol. Chem., September 10, 2004; 279(37): 38770 - 38778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Mitchell, E. Lee, M. L. Garcia, and M. M. Stephan Structure and Function of Extracellular Loop 4 of the Serotonin Transporter as Revealed by Cysteine-scanning Mutagenesis J. Biol. Chem., June 4, 2004; 279(23): 24089 - 24099. [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]
|
|
|
|
|
|
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, F. Ghassemi, and G. Rudnick A Conformationally Sensitive Residue on the Cytoplasmic Surface of Serotonin Transporter J. Biol. Chem., November 30, 2001; 276(49): 45933 - 45938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Eshleman, K. Wolfrum, D. C. Mash, K. Christensen, and A. Janowsky Drug Interactions with the Dopamine Transporter in Cryopreserved Human Caudate J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 442 - 449. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Xiao, J. Wang, T. Tangen, and K. M. Giacomini A Novel Proton-Dependent Nucleoside Transporter, CeCNT3, from Caenorhabditis elegans Mol. Pharmacol., February 1, 2001; 59(2): 339 - 348. [Abstract] [Full Text]
|
|
|
|
|
|
S. Chalon, L. Garreau, P. Emond, L. Zimmer, M.-P. Vilar, J.-C. Besnard, and D. Guilloteau Pharmacological Characterization of (E)-N-(3-iodoprop-2-enyl)-2beta -Carbomethoxy-3beta -(4'-methylphenyl)nortropane as a Selective and Potent Inhibitor of the Neuronal Dopamine Transporter J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 648 - 654. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Pineyro and P. Blier Autoregulation of Serotonin Neurons: Role in Antidepressant Drug Action Pharmacol. Rev., September 1, 1999; 51(3): 533 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Barker, K. R. Moore, F. Rakhshan, and R. D. Blakely Transmembrane Domain I Contributes to the Permeation Pathway for Serotonin and Ions in the Serotonin Transporter J. Neurosci., June 15, 1999; 19(12): 4705 - 4717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Berfield, L. C. Wang, and M. E. A. Reith Which Form of Dopamine Is the Substrate for the Human Dopamine Transporter: the Cationic or the Uncharged Species? J. Biol. Chem., February 19, 1999; 274(8): 4876 - 4882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xu and M. E. A. Reith WIN 35,428 and Mazindol Are Mutually Exclusive in Binding to the Cloned Human Dopamine Transporter J. Pharmacol. Exp. Ther., August 1, 1997; 282(2): 920 - 927. [Abstract] [Full Text]
|
|
|
|
|
|
S. R. Tella, B. Ladenheim, and J. L. Cadet Differential Regulation of Dopamine Transporter after Chronic Self-administration of Bupropion and Nomifensine J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 508 - 513. [Abstract] [Full Text]
|
|
|
|
|
|
J. D. Ramamoorthy, S. Ramamoorthy, A. Papapetropoulos, J. D. Catravas, F. H. Leibach, and V. Ganapathy Cyclic AMP-independent Up-regulation of the Human Serotonin Transporter by Staurosporine in Choriocarcinoma Cells J. Biol. Chem., July 21, 1995; 270(29): 17189 - 17195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. G. Ni, J.-G. Chen, A. Androutsellis-Theotokis, C.-J. Huang, E. Moczydlowski, and G. Rudnick A Lithium-induced Conformational Change in Serotonin Transporter Alters Cocaine Binding, Ion Conductance, and Reactivity of Cys-109 J. Biol. Chem., August 10, 2001; 276(33): 30942 - 30947. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
