Quantitative autoradiography of the dopamine uptake complex in rat brain using [3H]GBR 12935: binding characteristics - PubMed (original) (raw)
Quantitative autoradiography of the dopamine uptake complex in rat brain using [3H]GBR 12935: binding characteristics
E K Richfield. Brain Res. 1991.
Free article
Abstract
The dopamine uptake complex was examined in the rat central nervous system using [3H]GBR 12935 and in vitro quantitative autoradiography to determine all binding data. [3H]GBR 12935 labels two unique binding sites, the dopamine uptake complex and a piperazine acceptor site. These two sites differ in their pharmacologic properties, anatomical distributions, densities, and response to lesions. Using appropriate binding conditions, [3H]GBR 12935 can be used to specifically label the dopamine uptake complex. [3H]GBR 12935 labeled a single binding site with characteristics of the dopamine uptake complex when mazindol (25 microM) was used as a blank. The specific binding and autoradiographic appearance of [3H]GBR 12935 to the dopamine uptake complex was improved by including trans-flupentixol (0.75 microM) to displace binding to a previously described piperazine acceptor site, recently determined to be a site on cytochrome P450IID1. Binding was saturable and reversible to the dopamine uptake complex. The equilibrium dissociation constant (1.4 +/- 0.7 nM), maximal number of binding sites (6.0 +/- 1.3 pmol/mg protein), and Hill coefficient (1.1 +/- 0.1) of [3H]GBR 12935 in rat striatum using mazindol to define non-specific binding was not significantly altered by the inclusion of trans-flupentixol (0.75 microM). Using GBR 12909 as a blank produced a greater maximal number of binding sites (8.4 +/- 2.3 pmol/mg protein), but no significant difference in the equilibrium dissociation constant (1.6 +/- 0.3 nM) or Hill coefficient (1.1 +/- 0.1). A series of drugs that bind to the dopamine uptake complex displaced [3H]GBR 12935 in a rank order consistent with other binding and behavioral studies of this complex. The rank order of these drugs was GBR 12909 greater than mazindol greater than nomifensine greater than benztropine greater than desipramine greater than amphetamine greater than dopamine; all these drugs displayed a Hill coefficient near one and were best modeled as a single site. Cocaine and WIN 35,428 (a cocaine congener) were unique in their competition for [3H]GBR 12935 binding, displaying biphasic curves, low Hill coefficients, and were best modeled as two site fits. Lesioning of the dopaminergic median forebrain bundle resulted in a dramatic loss of the dopamine uptake complex in the striatum, nucleus accumbens, olfactory tubercle, and substantia nigra. Other dopaminergic projection areas were decreased to a lesser extent. Striatal ibotenate lesions did not decrease the density of the dopamine uptake complex, despite a large decrease in the dopamine D1 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
Similar articles
- High-affinity [3H]GBR 12783 binding to a specific site associated with the neuronal dopamine uptake complex in the central nervous system.
Bonnet JJ, Protais P, Chagraoui A, Costentin J. Bonnet JJ, et al. Eur J Pharmacol. 1986 Jul 31;126(3):211-22. doi: 10.1016/0014-2999(86)90050-6. Eur J Pharmacol. 1986. PMID: 3489625 - [3H]GBR-12935 binding to dopamine uptake sites in rat striatum.
Allard PO, Eriksson K, Ross SB, Marcusson JO. Allard PO, et al. Neuropsychobiology. 1990-1991;23(4):177-81. doi: 10.1159/000119449. Neuropsychobiology. 1990. PMID: 2130286 - The dopamine transporter and cytochrome P45OIID1 (debrisoquine 4-hydroxylase) in brain: resolution and identification of two distinct [3H]GBR-12935 binding proteins.
Niznik HB, Tyndale RF, Sallee FR, Gonzalez FJ, Hardwick JP, Inaba T, Kalow W. Niznik HB, et al. Arch Biochem Biophys. 1990 Feb 1;276(2):424-32. doi: 10.1016/0003-9861(90)90741-g. Arch Biochem Biophys. 1990. PMID: 2306106 - Dopaminergic 3H-agonist receptors in rat brain. New evidence on localization and pharmacology.
Bacopoulos NG. Bacopoulos NG. Life Sci. 1984 Jan 23;34(4):307-15. doi: 10.1016/0024-3205(84)90617-9. Life Sci. 1984. PMID: 6363861 Review. - Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake.
Wightman RM, Zimmerman JB. Wightman RM, et al. Brain Res Brain Res Rev. 1990 May-Aug;15(2):135-44. doi: 10.1016/0165-0173(90)90015-g. Brain Res Brain Res Rev. 1990. PMID: 2282449 Review.
Cited by
- Molecular fMRI of Serotonin Transport.
Hai A, Cai LX, Lee T, Lelyveld VS, Jasanoff A. Hai A, et al. Neuron. 2016 Nov 23;92(4):754-765. doi: 10.1016/j.neuron.2016.09.048. Epub 2016 Oct 20. Neuron. 2016. PMID: 27773583 Free PMC article. - Sampling phasic dopamine signaling with fast-scan cyclic voltammetry in awake, behaving rats.
Fortin SM, Cone JJ, Ng-Evans S, McCutcheon JE, Roitman MF. Fortin SM, et al. Curr Protoc Neurosci. 2015 Jan 5;70:7.25.1-7.25.20. doi: 10.1002/0471142301.ns0725s70. Curr Protoc Neurosci. 2015. PMID: 25559005 Free PMC article. - Primary food reward and reward-predictive stimuli evoke different patterns of phasic dopamine signaling throughout the striatum.
Brown HD, McCutcheon JE, Cone JJ, Ragozzino ME, Roitman MF. Brown HD, et al. Eur J Neurosci. 2011 Dec;34(12):1997-2006. doi: 10.1111/j.1460-9568.2011.07914.x. Epub 2011 Nov 29. Eur J Neurosci. 2011. PMID: 22122410 Free PMC article. - Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders.
Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K, Ohira K, Toyama K, Kanzaki K, Fukunaga K, Sudo Y, Ichinose H, Ikeda M, Iwata N, Ozaki N, Suzuki H, Higuchi M, Suhara T, Yuasa S, Miyakawa T. Yamasaki N, et al. Mol Brain. 2008 Sep 10;1:6. doi: 10.1186/1756-6606-1-6. Mol Brain. 2008. PMID: 18803808 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous