Substrate-Dependent Ligand Inhibition of the Human Organic Cation Transporter OCT2
نویسندگان
چکیده
منابع مشابه
Substrate-dependent ligand inhibition of the human organic cation transporter OCT2.
Organic cation transporter 2 (OCT2) mediates the initial step in renal secretion of organic cations: uptake from the blood, across the basolateral membrane, and into the renal proximal tubule cells. Because of its potential as a target for unwanted drug-drug interactions (DDIs), considerable attention has been directed toward understanding the basis of OCT2 selectivity. These studies typically ...
متن کاملSubstrate-Dependent Inhibition of the Human Organic Cation Transporter OCT2: A Comparison of Metformin with Experimental Substrates
The importance of the organic cation transporter OCT2 in the renal excretion of cationic drugs raises the possibility of drug-drug interactions (DDIs) in which an inhibitor (perpetrator) drug decreases OCT2-dependent renal clearance of a victim (substrate) drug. In fact, there are clinically significant interactions for drugs that are known substrates of OCT2 such as metformin. To identify drug...
متن کاملMultiple mechanisms of ligand interaction with the human organic cation transporter, OCT2.
OCT2 is the entry step for organic cation (OC) secretion by renal proximal tubules. Although many drugs inhibit OCT2 activity, neither the mechanistic basis of their inhibition nor their transport status is generally known. Using representatives of several structural classes of OCT2-inhibitory ligands described recently (Kido Y, Matsson P, Giacomini KM. J Med Chem 54: 4548-4558, 2011), we deter...
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Although metformin, a cationic agent for type II diabetes, shows its pharmacological effect in the liver, the drug is mainly eliminated into urine. The tissue selectivity based on the function of drug transporters is unclear. In the present study, the transport of metformin was examined using HEK293 cells transiently transfected with five human renal organic ion transporter cDNAs. Human OCT1 an...
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Human organic cation transporter 2 (OCT2/SLC22A2), which is specifically expressed in the kidney, plays critical roles in the renal secretion of cationic compounds. Tissue expression and membrane localization of OCT2 are closely related to the tissue distribution, pharmacological effects, and/or adverse effects of its substrate drugs. However, the molecular mechanisms underlying the kidney-spec...
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ژورنال
عنوان ژورنال: Journal of Pharmacology and Experimental Therapeutics
سال: 2013
ISSN: 0022-3565,1521-0103
DOI: 10.1124/jpet.113.203257