Linked Life Data

11561104

Source:http://linkedlifedata.com/resource/pubmed/id/11561104

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-9-18
pubmed:abstractText
Organic cation transporters (OCT1-3) play an important role in renal elimination of many drugs. The goals of this study were to 1) identify a cell culture model which constitutively expressed OCT2 that could be used to study the characteristics and regulation of this transporter, and 2) to study the mechanisms by which xenobiotics and hormones regulate the activity of OCT2. We characterized the endogenous organic cation transporter (OCT) activity in Madin-Darby canine kidney (MDCK) cells. The activity was localized to the basolateral membrane and was pH and membrane potential-dependent. The uptake of the model organic cation, tetraethylammonium, was saturable (Km, 19.5 +/- 4.6 microM; Vmax, 350 +/- 19.4 pmol/mg of protein/10 min) and was inhibited by known OCT inhibitors (e.g., cimetidine and quinidine). A cDNA fragment (711 base pairs) isolated by reverse transcriptase-polymerase chain reaction (RT-PCR) was greater than 83% identical to OCT2 cDNAs from mammalian species; no OCT1 or OCT3 was detected by RT-PCR, suggesting that OCT2 may be the primary basolateral OCT in MDCK. OCT2 mRNA levels were increased significantly following exposure of MDCK to the steroid hormones, dexamethasone (2.0-fold), hydrocortisone (2.4-fold), and testosterone (1.8-fold) with comparable increases in activity. Other compounds tested, including the cytochrome P450 inducers, rifampicin, phenobarbital, and phenytoin, and the OCT substrates, verapamil and metformin, had no inducing effects. Collectively, these data indicate that MDCK can serve as a useful and convenient tool in screening candidate drugs for interaction with OCT2 and for studying the regulation of this transporter. Furthermore, our data demonstrate that steroid hormones induce the transcription of OCT2 in the kidney.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
392-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Functional characteristics and steroid hormone-mediated regulation of an organic cation transporter in Madin-Darby canine kidney cells.
pubmed:affiliation
Department of Biopharmaceutical Sciences, University of California San Francisco, San Francisco, California 94143-0446, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't