[3H]mazindol binding associated with neuronal dopamine and norepinephrine uptake sites

JA Javitch, RO Blaustein and SH Snyder

[3H]Mazindol labels neuronal dopamine uptake sites in corpus striatum membranes (KD = 18 nM) and neuronal norepinephrine uptake sites in cerebral cortex and submaxillary/sublingual gland membranes (KD = 4 nM). The potencies of various inhibitors of biogenic amine uptake in reducing [3H]mazindol binding in striatal membranes correlate with their potencies for inhibition of neuronal [3H]dopamine accumulation, whereas their potencies in reducing [3H]mazindol binding to cortical and salivary gland membranes correlate with their potencies for inhibition of neuronal [3H]norepinephrine accumulation. Similar to the dopamine and norepinephrine uptake systems, [3H]mazindol binding in all three tissues is dependent upon sodium (with potassium, lithium, rubidium, and Tris being ineffective substitutes) and chloride (with sulfate and phosphate being ineffective substitutes). In membranes of the cerebral cortex and salivary gland, half-maximal stimulation is observed at 50-80 mM NaCl, whereas in membranes of the corpus striatum half-maximal stimulation occurs at 240 mM NaCl. In striatal membranes NaCl increases the affinity of [3H]mazindol binding with no effect on the maximal number of sites. The enhancement of affinity is due to a selective slowing of the dissociation of the ligand from its binding site. The association of [3H]mazindol binding sites with neuronal dopamine uptake sites in the corpus striatum is further supported by the reduction of [3H]mazindol binding sites in striatal membranes following destruction of dopaminergic neurons by 6-hydroxydopamine. Similarly, the association of [3H]mazindol binding sites with neuronal norepinephrine uptake sites in cerebral cortex is supported by the reduction of [3H]mazindol binding to cortical membranes following destruction of noradrenergic neurons by N-(2-chloroethyl)-N-ethyl-2- bromobenzylamine.

Volume 26, Issue 1, pp. 35-44, 07/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				S. Padilla, R. S. Marshall, D. L. Hunter, S. Oxendine, V. C. Moser, S. B. Southerland, and R. B. Mailman Neurochemical Effects of Chronic Dietary and Repeated High-Level Acute Exposure to Chlorpyrifos in Rats Toxicol. Sci., November 1, 2005; 88(1): 161 - 171. [Abstract] [Full Text] [PDF]

				R. I. Desai, T. A. Kopajtic, D. French, A. H. Newman, and J. L. Katz Relationship between in Vivo Occupancy at the Dopamine Transporter and Behavioral Effects of Cocaine, GBR 12909 [1-{2-[Bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine], and Benztropine Analogs J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 397 - 404. [Abstract] [Full Text] [PDF]

				R. I. Desai, T. A. Kopajtic, M. Koffarnus, A. H. Newman, and J. L. Katz Identification of a Dopamine Transporter Ligand That Blocks the Stimulant Effects of Cocaine J. Neurosci., February 23, 2005; 25(8): 1889 - 1893. [Abstract] [Full Text] [PDF]

				A. Iwashita, K. Mihara, S. Yamazaki, S. Matsuura, J. Ishida, H. Yamamoto, K. Hattori, N. Matsuoka, and S. Mutoh A New Poly(ADP-Ribose) Polymerase Inhibitor, FR261529 [2-(4-Chlorophenyl)-5-quinoxalinecarboxamide], Ameliorates Methamphetamine-Induced Dopaminergic Neurotoxicity in Mice J. Pharmacol. Exp. Ther., September 1, 2004; 310(3): 1114 - 1124. [Abstract] [Full Text] [PDF]

				K. Mardon, O. Montagne, N. Elbaz, Z. Malek, A. Syrota, J.-L. Dubois-Rande, M. Meignan, and P. Merlet Uptake-1 Carrier Downregulates in Parallel with the {beta}-Adrenergic Receptor Desensitization in Rat Hearts Chronically Exposed to High Levels of Circulating Norepinephrine: Implications for Cardiac Neuroimaging in Human Cardiomyopathies J. Nucl. Med., September 1, 2003; 44(9): 1459 - 1466. [Abstract] [Full Text] [PDF]

				S. Purkerson-Parker, K. L. McDaniel, and V. C. Moser Dopamine Transporter Binding in the Rat Striatum Is Increased by Gestational, Perinatal, and Adolescent Exposure to Heptachlor Toxicol. Sci., December 1, 2001; 64(2): 216 - 223. [Abstract] [Full Text] [PDF]

				I. Sora, F. S. Hall, A. M. Andrews, M. Itokawa, X.-F. Li, H.-B. Wei, C. Wichems, K.-P. Lesch, D. L. Murphy, and G. R. Uhl Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference PNAS, April 24, 2001; 98(9): 5300 - 5305. [Abstract] [Full Text] [PDF]

				E. M. Adkins, E. L. Barker, and R. D. Blakely Interactions of Tryptamine Derivatives with Serotonin Transporter Species Variants Implicate Transmembrane Domain I in Substrate Recognition Mol. Pharmacol., March 1, 2001; 59(3): 514 - 523. [Abstract] [Full Text]

				S. R. Letchworth, H. R. Smith, L. J. Porrino, B. A. Bennett, H. M. L. Davies, T. Sexton, and S. R. Childers Characterization of a Tropane Radioligand, [3H]2beta -Propanoyl-3beta -(4-tolyl) Tropane ([3H]PTT), for Dopamine Transport Sites in Rat Brain J. Pharmacol. Exp. Ther., May 1, 2000; 293(2): 686 - 696. [Abstract] [Full Text]

				N. R. Zahniser, G. A. Larson, and G. A. Gerhardt In Vivo Dopamine Clearance Rate in Rat Striatum: Regulation by Extracellular Dopamine Concentration and Dopamine Transporter Inhibitors J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 266 - 277. [Abstract] [Full Text]

				K. Mardon, P. Merlet, A. Syrota, and B. Maziere Effects of 5-day hypoxia on cardiac adrenergic neurotransmission in rats J Appl Physiol, September 1, 1998; 85(3): 890 - 897. [Abstract] [Full Text] [PDF]

				I. Sora, C. Wichems, N. Takahashi, X.-F. Li, Z. Zeng, R. Revay, K.-P. Lesch, D. L. Murphy, and G. R. Uhl Cocaine reward models: Conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice PNAS, June 23, 1998; 95(13): 7699 - 7704. [Abstract] [Full Text] [PDF]

				M. Ungerer, F. Hartmann, M. Karoglan, A. Chlistalla, S. Ziegler, G. Richardt, M. Overbeck, H. Meisner, A. Schomig, and M. Schwaiger Regional In Vivo and In Vitro Characterization of Autonomic Innervation in Cardiomyopathic Human Heart Circulation, January 20, 1998; 97(2): 174 - 180. [Abstract] [Full Text] [PDF]

				S.-J. Zhu, M. P. Kavanaugh, M. S. Sonders, S. G. Amara, and N. R. Zahniser Activation of Protein Kinase C Inhibits Uptake, Currents and Binding Associated with the Human Dopamine Transporter Expressed in Xenopus Oocytes J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1358 - 1365. [Abstract] [Full Text]

				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]

				M. A. Nader, K. A. Grant, H. M. L. Davies, R. H. Mach, and S. R. Childers The Reinforcing and Discriminative Stimulus Effects of the Novel Cocaine Analog 2beta -Propanoyl-3beta -(4-Tolyl)-Tropane in Rhesus Monkeys J. Pharmacol. Exp. Ther., February 1, 1997; 280(2): 541 - 550. [Abstract] [Full Text]

				M. S. Sonders, S.-J. Zhu, N. R. Zahniser, M. P. Kavanaugh, and S. G. Amara Multiple Ionic Conductances of the Human Dopamine Transporter: The Actions of Dopamine and Psychostimulants J. Neurosci., February 1, 1997; 17(3): 960 - 974. [Abstract] [Full Text] [PDF]

				M. Ungerer, A. Chlistalla, and G. Richardt Upregulation of Cardiac Uptake1 Carrier in Ischemic and Nonischemic Rat Heart Circ. Res., June 1, 1996; 78(6): 1037 - 1043. [Abstract] [Full Text]

				J. Adair and F. Filloux Effects of Hypoxic-Ischemic Brain Damage on Dopaminergic Markers in the Neonatal Rat: A Regional Autoradiographic Analysis J Child Neurol, April 1, 1992; 7(2): 199 - 207. [Abstract] [PDF]

				S Shimada, S Kitayama, C. Lin, A Patel, E Nanthakumar, P Gregor, M Kuhar, and G Uhl Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA Science, October 25, 1991; 254(5031): 576 - 578. [Abstract] [PDF]

				J. Kilty, D Lorang, and S. Amara Cloning and expression of a cocaine-sensitive rat dopamine transporter Science, October 25, 1991; 254(5031): 578 - 579. [Abstract] [PDF]

				J. M. McIntosh, G. O. Corpuz, R. T. Layer, J. E. Garrett, J. D. Wagstaff, G. Bulaj, A. Vyazovkina, D. Yoshikami, L. J. Cruz, and B. M. Olivera Isolation and Characterization of a Novel Conus Peptide with Apparent Antinociceptive Activity J. Biol. Chem., October 13, 2000; 275(42): 32391 - 32397. [Abstract] [Full Text] [PDF]

				M. E. A. Reith, J. L. Berfield, L. C. Wang, J. V. Ferrer, and J. A. Javitch The Uptake Inhibitors Cocaine and Benztropine Differentially Alter the Conformation of the Human Dopamine Transporter J. Biol. Chem., July 27, 2001; 276(31): 29012 - 29018. [Abstract] [Full Text] [PDF]