Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0518 Transporter Info
Gene Name CACNA1A
Transporter Name Voltage-gated calcium channel alpha Cav2.1
Gene ID
773
UniProt ID
O00555
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Valproic Acid affects the expression of CACNA1A mRNA [3]

Regulation Mechanism

 Transcription Factor Info

  11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid

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

  DT Modulation1

 Cannabinoids results in increased abundance of 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid which affects the methylation of CACNA1A gene [18]

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 CACNA1A mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide

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

  DT Modulation1

 NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in decreased expression of CACNA1A mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of CACNA1A mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene affects the methylation of CACNA1A intron [20]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in decreased methylation of CACNA1A exon [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Benzo(a)pyrene results in increased methylation of CACNA1A promoter [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 Benzo(a)pyrene results in increased mutagenesis of CACNA1A gene [22]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

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

  DT Modulation1

 bisphenol A results in decreased expression of CACNA1A mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  Cadmium Chloride

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

  DT Modulation1

 Cadmium Chloride results in increased expression of CACNA1A mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  Cannabinoids

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

  DT Modulation1

 Cannabinoids results in increased abundance of 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid which affects the methylation of CACNA1A gene [18]

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 CACNA1A gene [24]

Regulation Mechanism

 Transcription Factor Info

  Copper

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

  DT Modulation1

 NSC 689534 binds to Copper which results in increased expression of CACNA1A mRNA [25]

Regulation Mechanism

 Transcription Factor Info

  coumarin

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

  DT Modulation1

 coumarin results in increased phosphorylation of CACNA1A protein [26]

Regulation Mechanism

 Transcription Factor Info

  cypermethrin

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

  DT Modulation1

 cypermethrin results in decreased expression of CACNA1A protein [16]

Regulation Mechanism

 Transcription Factor Info

  dorsomorphin

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

  DT Modulation1

 NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in decreased expression of CACNA1A mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of CACNA1A mRNA [7]

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 CACNA1A mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  mono-(2-ethylhexyl)phthalate

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

  DT Modulation1

 mono-(2-ethylhexyl)phthalate results in decreased expression of CACNA1A mRNA [27]

Regulation Mechanism

 Transcription Factor Info

  NSC 689534

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

  DT Modulation1

 NSC 689534 binds to Copper which results in increased expression of CACNA1A mRNA [25]

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 increased expression of CACNA1A mRNA [28]

Regulation Mechanism

 Transcription Factor Info

  Phenylmercuric Acetate

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

  DT Modulation1

 NOG protein co-treated with Phenylmercuric Acetate co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in decreased expression of CACNA1A mRNA [7]

Regulation Mechanism

 Transcription Factor Info

  Succimer

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

  DT Modulation1

 Succimer co-treated with Magnetite Nanoparticles results in increased expression of CACNA1A mRNA [29]

Regulation Mechanism

 Transcription Factor Info

  TL8-506

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

  DT Modulation1

 TL8-506 co-treated with IFNG protein results in increased expression of CACNA1A mRNA [30]

Regulation Mechanism

 Transcription Factor Info

  trichostatin A

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

  DT Modulation1

 trichostatin A results in increased expression of CACNA1A mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  triphenyl phosphate

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

  DT Modulation1

 triphenyl phosphate affects the expression of CACNA1A mRNA [31]

Regulation Mechanism

 Transcription Factor Info

  Vorinostat

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

  DT Modulation1

 NOG protein co-treated with Vorinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of CACNA1A mRNA [7]

Regulation Mechanism

 Transcription Factor Info

Mycotoxins

  Aflatoxin B1

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

  DT Modulation1

 Aflatoxin B1 results in increased methylation of CACNA1A intron [20]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Tretinoin

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

  DT Modulation1

 Tretinoin inhibits the expression of CACNA1A [1]

  Methotrexate

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

  DT Modulation1

 Methotrexate increases the expression of CACNA1A [2]

  Carbamazepine

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

  DT Modulation1

 Carbamazepine affects the expression of CACNA1A [3]

  Temozolomide

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

  DT Modulation1

 Temozolomide inhibits the expression of CACNA1A [4]

  Testosterone

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

  DT Modulation1

 Testosterone inhibits the expression of CACNA1A [5]

  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 CACNA1A [7]

  Flunarizine

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

  DT Modulation1

 Flunarizine inhibits the activity of CACNA1A [8], [9]

Drug Marketed but not Approved by US FDA

  Rotenone

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

  DT Modulation1

 Rotenone inhibits the expression of CACNA1A [6]

Drug in Phase 3 Trial

  Triclosan

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

  DT Modulation1

 Triclosan inhibits the expression of CACNA1A [14]

Drug in Phase 2 Trial

  Bisphenol A

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

  DT Modulation1

 Bisphenol A inhibits the expression of CACNA1A [13]

  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 CACNA1A [7]

Drug in Phase 1 Trial

  Trichostatin A

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

  DT Modulation1

 Trichostatin A increases the expression of CACNA1A [12]

  XEN007

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

  DT Modulation1

 XEN007 inhibits the activity of CACNA1A [17]

Natural Product

  Particulate Matter

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

  DT Modulation1

 Particulate Matter inhibits the expression of CACNA1A [10]

  Thapsigargin

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

  DT Modulation1

 Thapsigargin increases the expression of CACNA1A [11]

  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 CACNA1A [15]

Pesticide/Insecticide

  Cypermethrin

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

  DT Modulation1

 Cypermethrin inhibits the expression of CACNA1A [16]
References
1 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
2 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
3 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.
4 Temozolomide induces activation of Wnt/beta-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278.
5 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384.
6 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615.
7 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.
8 Migraine prophylaxis with calcium antagonists: a haemodynamic study using transcranial Doppler ultrasound. Rev Neurol. 2004 Feb 16-29;38(4):316-9.
9 Positive Allosteric Interaction of Structurally Diverse T-Type Calcium Channel Antagonists. Cell Biochem Biophys. 2009 Jul 7.
10 Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers. Inhal Toxicol. 2007 Nov;19(14):1107-19.
11 The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells. Neurotoxicology. 2009 May;30(3):368-76.
12 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
13 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
14 Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 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.
16 Proteomic profiling reveals neuronal ion channel dysregulation and cellular responses to DNA damage-induced cell cycle arrest and senescence in human neuroblastoma SH-SY5Y cells exposed to cypermethrin. Neurotoxicology. 2022 Dec;93:71-83.
17 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
18 Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics. 2018;13(12):1208-1221.
19 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.
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 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
22 Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014;775-776:48-54.
23 High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
24 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
25 A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo. Free Radic Biol Med. 2011 Jan 1;50(1):110-21.
26 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022;449:116110.
27 Alteration of the N(6)-methyladenosine epitranscriptomic profile in synthetic phthalate-treated human induced pluripotent stem cell-derived endothelial cells. Epigenomics. 2022;14(19):1139-1155.
28 A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
29 DMSA-Coated Iron Oxide Nanoparticles Greatly Affect the Expression of Genes Coding Cysteine-Rich Proteins by Their DMSA Coating. Chem Res Toxicol. 2015;28(10):1961-74.
30 Combinations of Toll-like receptor 8 agonist TL8-506 activate human tumor-derived dendritic cells. J Immunother Cancer. 2022;10(6).
31 Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60-69 Years of Age: Evidence from the China BAPE Study. Environ Health Perspect. 2023;131(4):47009.

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