Differential effects of psychoactive substances on human wildtype and polymorphic T356M dopamine transporters (DAT).

Brain / metabolism Dopamine / metabolism Dopamine Plasma Membrane Transport Proteins / genetics HEK293 Cells Humans Psychotropic Drugs / pharmacology
DAT polymorphism Designer drugs Dopamine reuptake transporter

Journal

Toxicology
ISSN: 1879-3185
Titre abrégé: Toxicology
Pays: Ireland
ID NLM: 0361055

Informations de publication

Date de publication:
15 06 2019
Historique:
received: 11 02 2019
revised: 29 03 2019
accepted: 18 04 2019
pubmed: 23 4 2019
medline: 4 4 2020
entrez: 23 4 2019
Statut: ppublish

Résumé

Many psychoactive substances affect the human dopamine (DA) reuptake transporter (hDAT). Polymorphisms in the encoding gene could affect the functionality of the transporter and consequently alter effects of psychotropic and recreational drugs. Recently, a T356 M single nucleotide polymorphism in the human SLC6A3 gene was described, which resulted in functional impairments of DA uptake. Therefore, we investigated the effects of 10 psychoactive substances (0.01-1000 μM)) on DA uptake in human embryonic kidney (HEK) 293 cells transiently overexpressing wildtype (WT) or T356 M hDAT. Our data shows that T356 M hDAT has a 3 times lower V

Identifiants

DOI: 10.1016/j.tox.2019.04.012 PMID: 31009648
pubmed: 31009648
pii: S0300-483X(19)30128-3
doi: 10.1016/j.tox.2019.04.012
pii:
doi:

Substances chimiques

Dopamine Plasma Membrane Transport Proteins 0
Psychotropic Drugs 0
Dopamine VTD58H1Z2X

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

69-75

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Anne Zwartsen (A)

Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands; Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, P.O. Box 85.500, NL-3508, GA, Utrecht, the Netherlands.

Carlijn H C Litjens (CHC)

Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands.

Laura Hondebrink (L)

Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, P.O. Box 85.500, NL-3508, GA, Utrecht, the Netherlands.

Jeroen J M W van den Heuvel (JJMW)

Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands.

Rick Greupink (R)

Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands.

Frans G M Russel (FGM)

Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands.

Dylan W de Lange (DW)

Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, P.O. Box 85.500, NL-3508, GA, Utrecht, the Netherlands.

Juliette Legler (J)

Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.

Jan B Koenderink (JB)

Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands.

Remco H S Westerink (RHS)

Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. Electronic address: r.westerink@uu.nl.

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Classifications MeSH

questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Differential effects of psychoactive...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Phénols › Catéchols › Catécholamines › Dopamine › Differential effects of psychoactive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Transporteurs de la dopamine › Differential effects of psychoactive...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Differential effects of psychoactive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Differential effects of psychoactive...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Psychoanaleptiques › Differential effects of psychoactive...