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Pharm Res. 2002 Jan;19(1):34-41.

Transport activity of human MRP3 expressed in Sf9 cells: comparative studies with rat MRP3.

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1
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.

Abstract

PURPOSE:

Multidrug resistance-associated protein 3 (MRP3) was initially cloned as a hepatic transporter induced under cholestatic/ hyperbilirubinemic conditions. In the present study, transport property of human MRP3 (hMRP3) was compared with that of rat MRP3 (rMRP3).

METHODS:

Adenosine 5' triphosphate (ATP)-dependent uptake of several organic anions into the membrane vesicles isolated from the Sf9 cells expressing hMRP3 and rMRP3 was measured by rapid filtration technique.

RESULTS:

ATP-dependent uptake of glucuronide conjugates, glutathione conjugates. and [3H]methotrexate (MTX) was stimulated by infection of cDNAs for hMRP3 and rMRP3. The mean (+/- SE) Km values for the uptake of 17beta estradiol 17beta-D-glucuronide ([3H]E(2)17 betaG) by hMRP3 and rMRP3 were 42.9 +/- 4.3 microM and 33.4 +/- 2.2 microM, respectively. Although the Ki values of glucuronides on the uptake of E217betaG were similar in humans and rats, hMRP3 exhibited higher Ki values toward MTX. In addition, although glycocholate and taurolithocholate 3-sulfate (TLC-S) were transported by both hMRP3 and rMRP3, taurocholate was only transported to a significant degree by rMRP3. Moreover, the inhibitory effect of taurocholate and glycocholate on the transport of E(2)17beta3G was much more potent in rMRP3 compared to hMRP3.

CONCLUSION:

Collectively, the substrate specificity of hMRP3 resembles that of rMRP3 although differences were observed, particularly in bile acid transport.

PMID:
11837698
DOI:
10.1023/a:1013699130991
[Indexed for MEDLINE]

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