In:
American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 276, No. 4 ( 1999-04-01), p. G1037-G1042
Abstract:
The rat liver organic anion transporting polypeptide (Oatp1) has been extensively characterized mainly in the Xenopus laevis expression system as a polyspecific carrier transporting organic anions (bile salts), neutral compounds, and even organic cations. In this study, we extended this characterization using a mammalian expression system and confirm the basolateral hepatic expression of Oatp1 with a new antibody. Besides sulfobromophthalein [Michaelis-Menten constant ( K m ) of ∼3 μM], taurocholate ( K m of ∼32 μM), and estradiol- 17β-glucuronide ( K m of ∼4 μM), substrates previously shown to be transported by Oatp1 in transfected HeLa cells, we determined the kinetic parameters for cholate ( K m of ∼54 μM), glycocholate ( K m of ∼54 μM), estrone-3-sulfate ( K m of ∼11 μM), CRC-220 ( K m of ∼57 μM), ouabain ( K m of ∼3,000 μM), and ochratoxin A ( K m of ∼29 μM) in stably transfected Chinese hamster ovary (CHO) cells. In addition, three new substrates, taurochenodeoxycholate ( K m of ∼7 μM), tauroursodeoxycholate ( K m of ∼13 μM), and dehydroepiandrosterone sulfate ( K m of ∼5 μM), were also investigated. The results establish the polyspecific nature of Oatp1 in a mammalian expression system and definitely identify conjugated dihydroxy bile salts and steroid conjugates as high-affinity endogenous substrates of Oatp1.
Type of Medium:
Online Resource
ISSN:
0193-1857
,
1522-1547
DOI:
10.1152/ajpgi.1999.276.4.G1037
Language:
English
Publisher:
American Physiological Society
Publication Date:
1999
detail.hit.zdb_id:
1477329-6
SSG:
12
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