Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0440 Transporter Info
Gene Name SLC6A1
Transporter Name Sodium- and chloride-dependent GABA transporter 1
Gene ID
6529
UniProt ID
P30531
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Tiagabine results in decreased activity of SLC6A1 protein [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Valproic Acid affects the expression of SLC6A1 mRNA [28]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC6A1 3' UTR [19]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene affects the methylation of SLC6A1 5' UTR [19]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of SLC6A1 exon [19]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 Benzo(a)pyrene results in increased methylation of SLC6A1 promoter [19]

Regulation Mechanism

 Transcription Factor Info

  2-palmitoylglycerol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 2-palmitoylglycerol results in increased expression of SLC6A1 mRNA [18]

Regulation Mechanism

 Transcription Factor Info

  benzo(e)pyrene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 benzo(e)pyrene results in increased methylation of SLC6A1 intron [20]

Regulation Mechanism

 Transcription Factor Info

  CGP 52608

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 CGP 52608 promotes the reaction RORA protein binds to SLC6A1 gene [21]

Regulation Mechanism

 Transcription Factor Info

  entinostat

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 entinostat results in increased expression of SLC6A1 mRNA [11]

Regulation Mechanism

 Transcription Factor Info

  ethyl-p-hydroxybenzoate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 ethyl-p-hydroxybenzoate results in decreased expression of SLC6A1 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  ferrous chloride

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 ferrous chloride results in decreased expression of SLC6A1 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  gamma-Aminobutyric Acid

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Niflumic Acid inhibits the reaction SLC6A1 protein results in increased uptake of gamma-Aminobutyric Acid [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 SLC6A1 protein results in increased uptake of gamma-Aminobutyric Acid [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 SLC6A1 results in increased export of gamma-Aminobutyric Acid [25]

Regulation Mechanism

 Transcription Factor Info

  Methapyrilene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Methapyrilene results in increased methylation of SLC6A1 intron [20]

Regulation Mechanism

 Transcription Factor Info

  Niflumic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Niflumic Acid inhibits the reaction SLC6A1 protein results in increased uptake of gamma-Aminobutyric Acid [24]

Regulation Mechanism

 Transcription Factor Info

  N-Nitrosopyrrolidine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 N-Nitrosopyrrolidine results in decreased expression of SLC6A1 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  Okadaic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Okadaic Acid results in decreased expression of SLC6A1 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  perfluorooctane sulfonic acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 perfluorooctane sulfonic acid results in decreased expression of SLC6A1 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  perfluorooctanoic acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 perfluorooctanoic acid results in decreased expression of SLC6A1 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenite results in decreased expression of SLC6A1 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

Nanoparticle

  perfluoro-n-nonanoic acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 perfluoro-n-nonanoic acid results in decreased expression of SLC6A1 mRNA [15]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Tiagabine

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tiagabine inhibits the activity of SLC6A1 [2], [3]

Cell System

 Human embryonic kidney 293 cells (HEK293)-GABT1

  Cyclosporine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cyclosporine inhibits the expression of SLC6A1 [4]

  Estradiol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Estradiol inhibits the expression of SLC6A1 [4]

  Troglitazone

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Troglitazone inhibits the expression of SLC6A1 [5]

  Bosentan

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Bosentan affects the expression of SLC6A1 [6]

  Doxorubicin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Doxorubicin inhibits the expression of SLC6A1 [7]

  Valproic Acid

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Valproic Acid increases the expression of SLC6A1 [8]

Drug in Phase 2 Trial

  MS-275

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 MS-275 increases the expression of SLC6A1 [11]

Drug in Phase 1 Trial

  Sodium arsenite

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sodium arsenite inhibits the expression of SLC6A1 [13]

Investigative Drug

  Hinokinin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Hinokinin inhibits the transportation of Gamma-aminobutyric acid by SLC6A1 [1]

Affected Drug/Substrate

 Gamma-aminobutyric acid Modulation Type Inhibition

Cell System

 Monkey kidney tissue Fibroblast-like cell lines (COS)7-GABT1

  ST-1535

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 ST-1535 inhibits the activity of SLC6A1 [17]

Natural Product

  Coal Ash

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Coal Ash inhibits the expression of SLC6A1 [9]

  Tobacco Smoke Pollution

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tobacco Smoke Pollution inhibits the expression of SLC6A1 [16]

Mycotoxins

  Aflatoxin B1

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 inhibits the expression of SLC6A1 [10]

  DT Modulation2

 Aflatoxin B1 affects the expression of SLC6A1 protein [4]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Aflatoxin B1 results in decreased methylation of SLC6A1 gene [10]

Regulation Mechanism

 Transcription Factor Info

Carcinogen

  Benzo(a)pyrene

            5 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of SLC6A1 [14]

Health and Environmental Toxicant

  Lead

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Lead affects the expression of SLC6A1 [12]

  Perfluorooctane sulfonic acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Perfluorooctane sulfonic acid inhibits the expression of SLC6A1 [15]
References
1 The lignan (-)-hinokinin displays modulatory effects on human monoamine and GABA transporter activities. J Nat Prod. 2013 Oct 25;76(10):1889-95.
2 Stereospecific synthesis and structure-activity relationships of unsymmetrical 4,4-diphenylbut-3-enyl derivatives of nipecotic acid as GAT-1 inhibitors. Bioorg Med Chem Lett. 2011 Jan 1;21(1):602-5.
3 Design, synthesis and SAR studies of GABA uptake inhibitors derived from 2-substituted pyrrolidine-2-yl-acetic acids. Bioorg Med Chem. 2015 Mar 15;23(6):1284-306.
4 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
5 Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
6 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
7 Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
8 Stem Cell Transcriptome Responses and Corresponding Biomarkers That Indicate the Transition from Adaptive Responses to Cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
9 Endothelial effects of emission source particles: acute toxic response gene expression profiles. Toxicol In Vitro. 2009 Feb;23(1):67-77.
10 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
11 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
12 RNA-Seq of Human Neural Progenitor Cells Exposed to Lead (Pb) Reveals Transcriptome Dynamics, Splicing Alterations and Disease Risk Associations. Toxicol Sci. 2017 Sep 1;159(1):251-265.
13 Cellular and Molecular Effects of Prolonged Low-Level Sodium Arsenite Exposure on Human Hepatic HepaRG Cells. Toxicol Sci. 2018 Apr 1;162(2):676-687.
14 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
15 Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA) increase triglyceride levels and decrease cholesterogenic gene expression in human HepaRG liver cells. Arch Toxicol. 2020 Sep;94(9):3137-3155.
16 Integration of transcriptome analysis with pathophysiological endpoints to evaluate cigarette smoke toxicity in an in vitro human airway tissue model. Arch Toxicol. 2021 May;95(5):1739-1761.
17 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization. J Med Chem. 2005 Nov 3;48(22):6887-96.
18 Direct effect of 2-palmitoyl glycerol on promotion of gamma aminobutyric acid synthesis in normal human fetal-derived astrocytes. FEBS Open Bio. 2023;13(7):1320-1332.
19 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
20 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
21 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
22 Risk assessment of parabens in a transcriptomics-based in vitro test. Chem Biol Interact. 2023;384:110699.
23 Adaptive cellular response of the substantia nigra dopaminergic neurons upon age-dependent iron accumulation. Aging Cell. 2022;21(9):e13694.
24 Novel properties of a mouse gamma-aminobutyric acid transporter (GAT4). J Membr Biol. 2005;203(2):65-82.
25 Mechanisms of GABA release from human astrocytes. Glia. 2011;59(11):1600-11.
26 A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
27 GABA transporter deficiency causes tremor, ataxia, nervousness, and increased GABA-induced tonic conductance in cerebellum. J Neurosci. 2005;25(12):3234-45.
28 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20.

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