Back to Search
Start Over
The Human Organic Cation Transporter (hOCT2) Recognizes the Degree of Substrate Ionization
The Human Organic Cation Transporter (hOCT2) Recognizes the Degree of Substrate Ionization
- Source :
- Journal of Biological Chemistry. 277:22491-22496
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- The organic cation transporter, OCT2, plays a role in renal secretion of a broad array of weak bases. To determine whether the degree of ionization of these compounds plays a role in their interaction with OCT2, we examined the influence of external pH values on the activity of the human ortholog of OCT2, as expressed in Chinese hamster ovary-K1 cells. Importantly, changing the pH value from 7.0 to 8.0 had no effect on the rate of transport of the fixed cations, tetraethylammonium and 1-methyl-4-phenylpyridinium, i.e. the pH value did not have an effect upon the transporter itself. Cimetidine (pK(a) 6.92), a competitive inhibitor of hOCT2, displayed a 3.5-fold increase in IC(50) as pH values increased from 7 to 8. hOCT2-mediated cimetidine transport decreased over this pH range, the consequence of an increase in K(t) and decrease in J(max) at the higher pH value. The weak bases trimethoprim and 4-phenylpyridine showed a similar pattern of pH-sensitive interaction with hOCT2. The non-ionizable sterol, corticosterone, also inhibited hOCT2 activity, although it was neither competitive in nature nor was it sensitive to pH in the manner observed with weak bases. We conclude that the degree of ionization plays a critical role in binding of substrate to organic cation transporters.
- Subjects :
- Time Factors
Organic Cation Transport Proteins
Pyridines
Stereochemistry
CHO Cells
Transfection
Binding, Competitive
Biochemistry
Trimethoprim
Chinese hamster
Substrate Specificity
Degree of ionization
Inhibitory Concentration 50
chemistry.chemical_compound
Cricetinae
Animals
Enzyme Inhibitors
Molecular Biology
Ions
Binding Sites
Organic cation transport proteins
Tetraethylammonium
Dose-Response Relationship, Drug
biology
Chemistry
Anti-Inflammatory Agents, Non-Steroidal
Organic Cation Transporter 2
Substrate (chemistry)
Biological Transport
Transporter
Cell Biology
Hydrogen-Ion Concentration
biology.organism_classification
Sterol
Kinetics
Renal physiology
biology.protein
Folic Acid Antagonists
Cimetidine
Corticosterone
Protein Binding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 277
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....3c4737168abc3211d2aae20518f90d57
- Full Text :
- https://doi.org/10.1074/jbc.m203114200