Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0082 Transporter Info
Gene Name SLC12A1
Transporter Name Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
Gene ID
6557
UniProt ID
Q13621
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

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 decreased methylation of SLC12A1 gene [22]

Regulation Mechanism

 Transcription Factor Info

Chemical Compound

  DT Modulation1

 tris(1,3-dichloro-2-propyl)phosphate results in decreased activity of SLC12A1 protein [20]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene affects the methylation of SLC12A1 promoter [23]

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 SLC12A1 gene [24]

Regulation Mechanism

 Transcription Factor Info

  Fulvestrant

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

  DT Modulation1

 Fulvestrant results in decreased methylation of SLC12A1 gene [25]

Regulation Mechanism

 Transcription Factor Info

  S-(1,2-dichlorovinyl)cysteine

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

  DT Modulation1

 S-(1,2-dichlorovinyl)cysteine co-treated with Lipopolysaccharides results in increased expression of SLC12A1 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Bumetanide

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

  DT Modulation1

 Bumetanide blocks the activity of SLC12A1 [1], [2]

  DT Modulation2

 Bumetanide inhibits the activity of SLC12A1 [5]

  Furosemide

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

  DT Modulation1

 Furosemide blocks the activity of SLC12A1 [3]

  DT Modulation2

 Furosemide induces the activity of SLC12A1 [4]

  Chloroquine

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

  DT Modulation1

 Chloroquine inhibits the expression of SLC12A1 [6]

  Zoledronic Acid

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

  DT Modulation1

 Zoledronic Acid inhibits the expression of SLC12A1 [7]

  Estradiol

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

  DT Modulation1

 Estradiol inhibits the expression of SLC12A1 [8]

  Torasemide

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

  DT Modulation1

 Torsemide blocks the activity of SLC12A1 [9], [10], [11]

  Bendroflumethiazide

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

  DT Modulation1

 Bendroflumethiazide blocks the activity of SLC12A1 [12]

  Hydroflumethiazide

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

  DT Modulation1

 Hydroflumethiazide blocks the activity of SLC12A1 [12]

  Methyclothiazide

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

  DT Modulation1

 Methyclothiazide blocks the activity of SLC12A1 [12]

  Ethacrynic Acid

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

  DT Modulation1

 Ethacrynic acid blocks the activity of SLC12A1 [13], [14]

  Ethacrynate sodium

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

  DT Modulation1

 Ethacrynate sodium modulates the activity of SLC12A1 [15]

  Potassium chloride

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

  DT Modulation1

 Potassium chloride modulates the activity of SLC12A1 [15]

  Trichlormethiazide

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

  DT Modulation1

 Trichloromethiazide blocks the activity of SLC12A1 [16]

  Chlorthalidone

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

  DT Modulation1

 Chlorthalidone blocks the activity of SLC12A1 [17]

  Vasopressin

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

  DT Modulation1

 Vasopressin induces the activity of SLC12A1 [18]

  Hydrochlorothiazide

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

  DT Modulation1

 Hydrochlorothiazide induces the activity of SLC12A1 [4]

Drug in Preclinical Test

  Nitric oxide

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

  DT Modulation1

 Nitric oxide inhibits the activity of SLC12A1 [21]

Environmental toxicant

  Zinc Oxide

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

  DT Modulation1

 Zinc Oxide inhibits the expression of SLC12A1 [19]

Health and Environmental Toxicant

  tris(1,3-dichloro-2-propyl)phosphate

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

  DT Modulation1

 tris(1,3-dichloro-2-propyl)phosphate inhibits the activity of SLC12A1 [20]
References
1 Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37.
2 Effect of L-ascorbate on chloride transport in freshly excised sinonasal epithelia. Am J Rhinol Allergy. 2009 May-Jun;23(3):294-9.
3 Update of diuretics in the treatment of hypertension. Am J Ther. 2007 Mar-Apr;14(2):154-60.
4 Long-term adaptation of renal ion transporters to chronic diuretic treatment. Am J Nephrol. 2004 Nov-Dec;24(6):595-605.
5 Localization and functional characterization of the human NKCC2 isoforms. Acta Physiol (Oxf). 2010 Jul 1;199(3):327-38.
6 Chronic use of chloroquine disrupts the urine concentration mechanism by lowering cAMP levels in the inner medulla. Am J Physiol Renal Physiol. 2012 Sep 15;303(6):F900-5.
7 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
8 17 beta-Estradiol Activates HSF1 via MAPK Signaling in ER alpha-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533.
9 Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
10 Effects of loop diuretics on angiotensin II-stimulated vascular smooth muscle cell growth. Nephrol Dial Transplant. 2001;16 Suppl 1:14-7.
11 Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats. Hypertension. 1999 Jul;34(1):138-43.
12 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
13 Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of trabecular meshwork cells. Am J Physiol. 1995 Apr;268(4 Pt 1):C1067-74.
14 Inhibition of Na-K-2Cl cotransport and bumetanide binding by ethacrynic acid, its analogues, and adducts. Am J Physiol. 1993 May;264(5 Pt 1):C1270-7.
15 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
16 Function and regulation of epithelial sodium transporters in the kidney of a salt-sensitive hypertensive rat model. J Hypertens. 2007 May;25(5):1065-72.
17 The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52.
18 Short-term stimulation of the renal Na-K-Cl cotransporter (NKCC2) by vasopressin involves phosphorylation and membrane translocation of the protein. J Biol Chem. 2003 Jul 18;278(29):26946-51.
19 Effects of zinc oxide nanoparticles on human coronary artery endothelial cells. Food Chem Toxicol. 2016 Jul;93:138-44.
20 Effect of the flame retardant tris (1,3-dichloro-2-propyl) phosphate (TDCPP) on Na+-K+-ATPase and Cl- transport in HeLa cells. Toxicol Mech Methods. 2018 Oct;28(8):599-606.
21 Role of nitric oxide in the NKCC2 hyperactivity of Dahl "salt-sensitive" rats. Arch Mal Coeur Vaiss. 2004 Jul-Aug;97(7-8):731-3.
22 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
23 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
24 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
25 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
26 The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine inhibits lipopolysaccharide-induced inflammation transcriptomic pathways and cytokine secretion in a macrophage cell model. Toxicol In Vitro. 2022;84:105429.

If you find any error in data or bug in web service, please kindly report it to Dr. Li and Dr. Fu.