Linked Life Data

8779894

Source:http://linkedlifedata.com/resource/pubmed/id/8779894

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2 Pt 2
pubmed:dateCreated
1996-12-20
pubmed:abstractText
Although substantial evidence indicates that estradiol-17 beta (E2) is conjugated to the glucuronide in the kidney and then excreted by a direct tubular secretory route and that the liver transports E2 glucuronides via carrier-mediated mechanisms, the transporters involved in these processes have not been identified. The so-called "organic anion-transporting polypeptide" (i.e., oatp) has a number of known substrates, including bromosulfophthalein (BSP) and taurocholic acid (TCA) (E. Jacquemin, B. Hagenbuch, B. Stieger, A. W. Wolkoff, and P. J. Meier. Proc. Natl. Acad. Sci. USA 91: 133-137, 1994). In a companion study, we determined that steroid hormones represent a class of hormones that interact strongly with oatp when the latter is transiently expressed in vitro. Here, we studied more extensively steroids and steroid anion conjugates as candidate oatp substrates. In HeLa cell monolayers transfected with a full-length oatp cDNA, [3H]estradiol 17 beta-D-glucuronide ([3H]E2-17G) was transported with a signal-to-noise ratio of 15:1 over that of monolayers transfected with a control plasmid. The affinity of oatp for [3H]E2-17G was significantly higher than that for TCA (K(m) of 3 microM vs. 27 microM, respectively). In contrast to E2-17G, unconjugated estradiol (E2) was not significantly transported by oatp. Several unconjugated steroids and anionic steroid conjugates were tested for their ability to compete with tracer E2-17G for oatp-mediated transport. Conjugation at the 17 or 3 position with the anion of a strong acid (sulfate) resulted in a greater degree of inhibition of tracer E2-17G transport than did conjugation at the 17 or 3 position with an uncharged group (acetate), suggesting that the strength of the negative charge at these positions is an important determinant of the affinity of a given steroid conjugate for oatp. We conclude that the preferred substrates for oatp are steroids with a strong 17- or 3-position anionic group. Since steroid sulfotransferases and glucuronosyltransferases are expressed in the proximal tubule, as is oatp, the transporter may serve as an apical exit pathway for steroids following their conjugation within the tubule cell.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F326-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Estradiol 17 beta-D-glucuronide is a high-affinity substrate for oatp organic anion transporter.
pubmed:affiliation
Department of Medicine, Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't