J. Konig et al., A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane, AM J P-GAST, 278(1), 2000, pp. G156-G164
Citations number
42
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
We cloned and expressed a new organic anion transporting polypeptide (OATP)
, termed human OATP2, (OATP-C, LST-1; symbol SLC21A6), involved in the upta
ke of various lipophilic anions into human liver. The cDNA encoding OATP2 c
omprised 2073 base pairs, corresponding to a protein of 691 amino acids, wh
ich were 44% identical to the known human OATP. An antibody directed agains
t the carboxy terminus localized OATP2 to the basolateral membrane of human
hepatocytes. Northern blot analysis indicated a strong expression of OATP2
only in human liver. Transport mediated by recombinant OATP2 and its local
ization were studied in stably transfected Madin-Darby canine kidney strain
II (MDCKII) and HEK293 cells. Confocal microscopy localized recombinant OA
TP2 protein to the lateral membrane of MDCKII cells. Substrates included 17
beta-glucuronosyl estradiol, monoglucuronosyl bilirubin, dehydroepiandrost
erone sulfate, and cholyltaurine. 17 beta-Glucuronosyl estradiol was a pref
erred substrate, with a Michaelis-Menten constant value of 8.2 mu M; its up
take was Na+ independent and was inhibited by sulfobromophthalein, with a i
nhibition constant value of 44 nM. Our results indicate that OATP2 is impor
tant for the uptake of organic anions, including bilirubin conjugates and s
ulfobromophthalein, in human liver.