Bumetanide

Overview

Description
A medication used to treat swelling from water retention.
Description
A medication used to treat swelling from water retention.
DrugBank ID
DB00887
Type
Small Molecule
US Approved
YES
Other Approved
YES
Clinical Trials
Phase 0
0
Phase 1
7
Phase 2
10
Phase 3
7
Phase 4
8
Therapeutic Categories
  • Diuretics
  • Sodium Potassium Chloride Symporter Inhibitors

Identification

Summary

Bumetanide is a sulfamyl diuretic used to treat edema in congestive heart failure, hepatic and renal disease, and nephrotic syndrome.

Brand Names
Bumex, Burinex
Generic Name
Bumetanide
DrugBank Accession Number
DB00887
Background

Bumetanide is a sulfamyl diuretic.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 364.416
Monoisotopic: 364.10929245
Chemical Formula
C17H20N2O5S
Synonyms
  • 3-(aminosulfonyl)-5-(butylamino)-4-phenoxybenzoic acid
  • 3-butylamino-4-(phenoxy)-5-sulfamoylbenzoic acid
  • 3-butylamino-4-phenoxy-5-sulfamoyl-benzoic acid
  • 3-butylamino-4-phenoxy-5-sulfamoylbenzoic acid
  • Bumetanida
  • Bumetanide
  • Bumetanidum
External IDs
  • CS 380
  • RO 10-6338
  • RO-10-6338

Pharmacology

Indication

For the treatment of edema associated with congestive heart failure, hepatic and renal disease including the nephrotic syndrome.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofEdema••••••••••••
Management ofEdema••••••••••••
Management ofEdema••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Bumetanide is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in patients in whom high doses of furosemide are ineffective. There is however no reason not to use bumetanide as a first choice drug. The main difference between the two substances is in bioavailability. Bumetanide has more predictable pharmacokinetic properties as well as clinical effect. In patients with normal renal function, bumetanide is 40 times more effective than furosemide.

Mechanism of action

Bumetanide interferes with renal cAMP and/or inhibits the sodium-potassium ATPase pump. Bumetanide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis.

TargetActionsOrganism
ASolute carrier family 12 member 1
inhibitor
Humans
ASolute carrier family 12 member 2
inhibitor
Humans
ASolute carrier family 12 member 4
inhibitor
Humans
ASolute carrier family 12 member 5
inhibitor
Humans
UCystic fibrosis transmembrane conductance regulator
antagonist
Humans
Absorption

Bumetanide is completely absorbed (80%), and the absorption is not altered when taken with food. Bioavailability is almost complete.

Volume of distribution

Not Available

Protein binding

97%

Metabolism

45% is secreted unchanged. Urinary and biliary metabolites are formed by oxidation of the N-butyl side chain.

Route of elimination

Oral administration of carbon-14 labeled Bumex to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Biliary excretion of Bumex amounted to only 2% of the administered dose.

Half-life

60-90 minutes

Clearance
  • 0.2 - 1.1 mL/min/kg [preterm and full-term neonates with respiratory disorders]
  • 2.17 mL/min/kg [neonates receiving bumetanide for volume overload]
  • 1.8 +/- 0.3 mL/min/kg [geriatric subjects]
  • 2.9 +/- 0.2 mL/min/kg [younger subjects]
Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Overdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.

Pathways
PathwayCategory
Bumetanide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirBumetanide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbaloparatideThe risk or severity of adverse effects can be increased when Bumetanide is combined with Abaloparatide.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Bumetanide.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Bumetanide.
AcebutololThe risk or severity of adverse effects can be increased when Bumetanide is combined with Acebutolol.
Food Interactions
  • Take with food. Food reduces irritation.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Images
International/Other Brands
Burinex (F. Hoffmann-La Roche Ltd.) / Fordiuran (LEO Pharma A/S) / Lunetoron (Daiichi Sankyo)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BumexTablet0.5 mg/1OralValidus Pharmaceuticals LLC1983-02-28Not applicableUS flag
BumexTablet0.5 mg/1OralGenentech, Inc.1983-02-282007-10-31US flag
BumexTablet2 mg/1OralValidus Pharmaceuticals LLC1983-02-28Not applicableUS flag
BumexTablet2 mg/1OralGenentech, Inc.1983-02-282007-10-31US flag
BumexTablet1 mg/1OralPhysicians Total Care, Inc.1996-04-042011-05-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BumetanideTablet2 mg/1OralEdenbridge Pharmaceuticals LLC.2015-10-15Not applicableUS flag
BumetanideTablet2 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs2007-10-16Not applicableUS flag
BumetanideInjection0.25 mg/1mLIntramuscular; IntravenousCivica, Inc.2022-03-07Not applicableUS flag
BumetanideTablet1 mg/1OralAvera McKennan Hospital2015-03-262017-05-24US flag
BumetanideTablet0.5 mg/1OralNCS HealthCare of KY, LLC dba Vangard Labs2017-10-18Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BURINEX TABLET 1 mgBumetanide (1 mg) + Bumetanide (1.0 mg)TabletOralZUELLIG PHARMA SDN. BHD.1988-03-05Not applicableSingapore flag
BURINEX TABLET 1 mgBumetanide (1 mg) + Bumetanide (1.0 mg)TabletOralZUELLIG PHARMA SDN. BHD.1988-03-05Not applicableSingapore flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BumexBumetanide (1 mg/1)TabletOralPhysicians Total Care, Inc.1996-04-042011-05-31US flag

Categories

ATC Codes
G01AE10 — Combinations of sulfonamidesC03CB02 — Bumetanide and potassiumC03EB02 — Bumetanide and potassium-sparing agentsC03CA02 — Bumetanide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylethers
Direct Parent
Diphenylethers
Alternative Parents
Aminobenzenesulfonamides / Diarylethers / Aminobenzoic acids / Benzenesulfonyl compounds / Benzoic acids / Phenylalkylamines / Aniline and substituted anilines / Phenoxy compounds / Phenol ethers / Benzoyl derivatives
show 9 more
Substituents
Amine / Amino acid / Amino acid or derivatives / Aminobenzenesulfonamide / Aminobenzoic acid / Aminobenzoic acid or derivatives / Aminosulfonyl compound / Aniline or substituted anilines / Aromatic homomonocyclic compound / Benzenesulfonamide
show 27 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
sulfonamide, benzoic acids, amino acid (CHEBI:3213)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
0Y2S3XUQ5H
CAS number
28395-03-1
InChI Key
MAEIEVLCKWDQJH-UHFFFAOYSA-N
InChI
InChI=1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23)
IUPAC Name
3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid
SMILES
CCCCNC1=C(OC2=CC=CC=C2)C(=CC(=C1)C(O)=O)S(N)(=O)=O

References

Synthesis Reference

Felt, P.W.; US. Patent 3,634,583; January 11, 1972; assigned to Lovens Kemiske Fabrik Produktionsaktieselskab, Denmark.

General References
Not Available
Human Metabolome Database
HMDB0015024
KEGG Drug
D00247
PubChem Compound
2471
PubChem Substance
46508147
ChemSpider
2377
BindingDB
25903
RxNav
1808
ChEBI
3213
ChEMBL
CHEMBL1072
ZINC
ZINC000003813061
Therapeutic Targets Database
DAP000361
PharmGKB
PA448682
PDBe Ligand
82U
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Bumetanide
PDB Entries
7s1x / 7s1y / 7smp
FDA label
Download (206 KB)
MSDS
Download (72.8 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableCoronavirus Disease 2019 (COVID‑19) / COVID / Hypertension1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentCritical Care / Fluid Shifts1somestatusstop reasonjust information to hide
Not AvailableRecruitingTreatmentAcute Decompensated Heart Failure (ADHF)1somestatusstop reasonjust information to hide
Not AvailableTerminatedDiagnosticAcute Decompensated Heart Failure (ADHF)1somestatusstop reasonjust information to hide
Not AvailableTerminatedTreatmentChronic Kidney Insufficiencies1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Teva parenteral medicines inc
  • Validus pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sandoz inc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Cardinal Health
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • F Hoffmann-La Roche Ltd.
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Sandhills Packaging Inc.
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
Dosage Forms
FormRouteStrength
TabletOral1.000 mg
InjectionIntramuscular; Intravenous0.25 mg/1mL
Injection, solutionIntramuscular; Intravenous0.25 mg/1mL
Injection, solutionIntravenous0.25 mg/1mL
TabletOral.5 mg/1
TabletOral0.5 mg/1
TabletOral2 mg/1
TabletOral1 mg/1
Capsule
TabletOral1 mg
TabletOral5 mg
TabletOral2 mg
Injection, solutionIntravenous0.5 mg/ml
InjectionIntramuscular; Intravenous0.5 mg/ml
TabletOral1 mg
TabletOral
SolutionIntravenous0.5000 mg
TabletOral1.00 mg
Prices
Unit descriptionCostUnit
Bumex 2 mg tablet1.65USD tablet
Bumetanide 2 mg tablet1.04USD tablet
Bumex 1 mg tablet0.98USD tablet
Bumex 0.5 mg tablet0.7USD tablet
Bumetanide 1 mg tablet0.51USD tablet
Bumetanide 0.5 mg tablet0.38USD tablet
Bumetanide 0.25 mg/ml vial0.25USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)230-231Felt, P.W.; US. Patent 3,634,583; January 11, 1972; assigned to Lovens Kemiske Fabrik Produktionsaktieselskab, Denmark.
water solubility>20 mg/mL (in base)Not Available
logP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0257 mg/mLALOGPS
logP3.44ALOGPS
logP2.42Chemaxon
logS-4.2ALOGPS
pKa (Strongest Acidic)4.69Chemaxon
pKa (Strongest Basic)2.7Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area118.72 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity95.78 m3·mol-1Chemaxon
Polarizability37.21 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9967
Blood Brain Barrier-0.6636
Caco-2 permeable-0.6492
P-glycoprotein substrateNon-substrate0.509
P-glycoprotein inhibitor INon-inhibitor0.8765
P-glycoprotein inhibitor IINon-inhibitor0.8103
Renal organic cation transporterNon-inhibitor0.8966
CYP450 2C9 substrateNon-substrate0.6368
CYP450 2D6 substrateNon-substrate0.7656
CYP450 3A4 substrateNon-substrate0.6059
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7344
Ames testNon AMES toxic0.6794
CarcinogenicityNon-carcinogens0.7294
BiodegradationNot ready biodegradable0.9837
Rat acute toxicity1.8148 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9319
hERG inhibition (predictor II)Non-inhibitor0.8591
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-000w-7198000000-9c32fd3e7109756cbcbb
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00lu-1694000000-dbf4d76ea1a12ee57935
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00lu-0594000000-78579410f8f6799b400b
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0009000000-2a72173931dce5701622
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0119000000-4abf1963718d72f73f59
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-9351000000-b43658e112020008b9f9
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-9100000000-4d303174266311856c28
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-9000000000-2d120289f52c86515bea
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0009000000-97827d479a3470c40d42
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-015c-0396000000-5edaaa0fcc7cd3681c24
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000x-0980000000-0b360ca9bf4e58649db7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-053s-0910000000-c5fc710abfdf5947bc62
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4j-0900000000-368c9661bc6dfd8a8d83
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-000x-0291000000-134f42a8645c2f1b9bc5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0009000000-e4d18d4c63310d0528db
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000x-0390000000-abfea32acc207ff88b1f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-053r-0930000000-cc33040126bfe7cb08fa
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a5a-0910000000-42b9627a1135073b6ce1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0ars-0900000000-d22f5ff182cd71ced792
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lu-0594000000-78579410f8f6799b400b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lu-1694000000-dbf4d76ea1a12ee57935
MS/MS Spectrum - , positiveLC-MS/MSsplash10-053s-2920000000-ecd6db66d16ce8f483b8
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-0009000000-6082dc141e96f2884dc9
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-1009000000-30be9acfa72f221163a1
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-0019000000-05023f04e55e3f5e1de1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03fr-4019000000-31aec091acafc5cf8269
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0lki-1489000000-2541c57ecccac8fe953c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-002f-9174000000-09ddce61c5dedf502471
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-202.1862591
predicted
DarkChem Lite v0.1.0
[M-H]-201.1089591
predicted
DarkChem Lite v0.1.0
[M-H]-182.65544
predicted
DeepCCS 1.0 (2019)
[M+H]+202.6577591
predicted
DarkChem Lite v0.1.0
[M+H]+202.0907591
predicted
DarkChem Lite v0.1.0
[M+H]+185.03035
predicted
DeepCCS 1.0 (2019)
[M+Na]+202.2088591
predicted
DarkChem Lite v0.1.0
[M+Na]+201.4214591
predicted
DarkChem Lite v0.1.0
[M+Na]+193.31616
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation (PubMed:21321328). Electrically silent transporter system (By similarity)
Specific Function
sodium
Gene Name
SLC12A1
Uniprot ID
Q13621
Uniprot Name
Solute carrier family 12 member 1
Molecular Weight
121449.13 Da
References
  1. Thakker RV: Chloride channels in renal disease. Adv Nephrol Necker Hosp. 1999;29:289-98. [Article]
  2. Karolyi L, Koch MC, Grzeschik KH, Seyberth HW: The molecular genetic approach to "Bartter's syndrome". J Mol Med (Berl). 1998 Apr;76(5):317-25. [Article]
  3. Thakker RV: The role of renal chloride channel mutations in kidney stone disease and nephrocalcinosis. Curr Opin Nephrol Hypertens. 1998 Jul;7(4):385-8. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  5. Long P, Mercer A, Begum R, Stephens GJ, Sihra TS, Jovanovic JN: 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. doi: 10.1074/jbc.M805322200. Epub 2009 Jan 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:16669787, PubMed:32081947, PubMed:32294086, PubMed:33597714, PubMed:35585053, PubMed:36239040, PubMed:36306358, PubMed:7629105). Plays a vital role in the regulation of ionic balance and cell volume (PubMed:16669787, PubMed:32081947, PubMed:32294086, PubMed:7629105)
Specific Function
ammonium channel activity
Gene Name
SLC12A2
Uniprot ID
P55011
Uniprot Name
Solute carrier family 12 member 2
Molecular Weight
131445.825 Da
References
  1. Panet R, Marcus M, Atlan H: Overexpression of the Na(+)/K(+)/Cl(-) cotransporter gene induces cell proliferation and phenotypic transformation in mouse fibroblasts. J Cell Physiol. 2000 Jan;182(1):109-18. [Article]
  2. Evans RL, Park K, Turner RJ, Watson GE, Nguyen HV, Dennett MR, Hand AR, Flagella M, Shull GE, Melvin JE: Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice. J Biol Chem. 2000 Sep 1;275(35):26720-6. [Article]
  3. Wall SM, Fischer MP, Mehta P, Hassell KA, Park SJ: Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD. Am J Physiol Renal Physiol. 2001 May;280(5):F913-21. [Article]
  4. Akar F, Jiang G, Paul RJ, O'Neill WC: Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle. Am J Physiol Cell Physiol. 2001 Aug;281(2):C579-84. [Article]
  5. Jiang G, Klein JD, O'Neill WC: Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism. Am J Physiol Cell Physiol. 2001 Dec;281(6):C1948-53. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:35759661). May contribute to cell volume homeostasis in single cells (PubMed:10913127, PubMed:34031912). May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity)
Specific Function
ATP binding
Gene Name
SLC12A4
Uniprot ID
Q9UP95
Uniprot Name
Solute carrier family 12 member 4
Molecular Weight
120648.73 Da
References
  1. Jean-Xavier C, Pflieger JF, Liabeuf S, Vinay L: Inhibitory postsynaptic potentials in lumbar motoneurons remain depolarizing after neonatal spinal cord transection in the rat. J Neurophysiol. 2006 Nov;96(5):2274-81. Epub 2006 Jun 28. [Article]
  2. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis (PubMed:12106695). As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (PubMed:24668262)
Specific Function
ammonium channel activity
Gene Name
SLC12A5
Uniprot ID
Q9H2X9
Uniprot Name
Solute carrier family 12 member 5
Molecular Weight
126182.49 Da
References
  1. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810)
Specific Function
ABC-type transporter activity
Gene Name
CFTR
Uniprot ID
P13569
Uniprot Name
Cystic fibrosis transmembrane conductance regulator
Molecular Weight
168139.895 Da
References
  1. Reddy MM, Quinton PM: Bumetanide blocks CFTR GCl in the native sweat duct. Am J Physiol. 1999 Jan;276(1 Pt 1):C231-7. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Specific Function
enzyme binding
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC: Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride. J Clin Invest. 2000 Sep;106(5):681-8. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774). It is strictly dependent on the extracellular presence of sodium (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774). It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate (PubMed:14660639, PubMed:34060352). Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321)
Specific Function
bile acid
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Hepatic sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier PJ: Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10629-33. [Article]
  2. Platte HD, Honscha W, Schuh K, Petzinger E: Functional characterization of the hepatic sodium-dependent taurocholate transporter stably transfected into an immortalized liver-derived cell line and V79 fibroblasts. Eur J Cell Biol. 1996 May;70(1):54-60. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Substrate activity was investigated in vitro.
General Function
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
Specific Function
alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. [Article]
  2. Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. [Article]
  3. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function
organic anion transmembrane transporter activity
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Organic anion transporter 3
Molecular Weight
59855.585 Da
References
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [Article]
  2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
Specific Function
organic anion transmembrane transporter activity
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Functions as a Na(+)-independent bidirectional multispecific transporter (PubMed:11327718, PubMed:18216183, PubMed:21446918, PubMed:28945155). Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively (PubMed:11327718, PubMed:25904762). Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates (PubMed:11327718, PubMed:18216183, PubMed:26377792, PubMed:28945155). Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways (PubMed:18216183, PubMed:26377792). Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood (PubMed:21446918). Involved in renal secretion and possible reabsorption of creatinine (PubMed:25904762, PubMed:28945155). Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate (PubMed:11327718, PubMed:26377792). Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified (PubMed:26377792)
Specific Function
alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
References
  1. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Horz JA, Honscha W, Petzinger E: Bumetanide is not transported by the Ntcp or by the oatp: evidence for a third organic anion transporter in rat liver cells. Biochim Biophys Acta. 1996 Apr 19;1300(2):114-8. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 05, 2024 18:59