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Multispecificity of Na+-dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles

Zimmerli, B. and Valantinas, J. and Meier, P. J.. (1989) Multispecificity of Na+-dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles. The Journal of Pharmacology and Experimental Therapeutics, Vol. 250, H. 1. pp. 301-308.

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Official URL: http://edoc.unibas.ch/dok/A5261784

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Abstract

To test the hypothesis of broad specificity of the hepatocellular bile acid uptake system(s) we investigated the kinetics and substrate specificity of Na+-dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles in the presence and absence of bovine serum albumin. Bovine serum albumin selectively stimulated the Na+-dependent portion of taurocholate uptake and decreased its apparent Km from 46 +/- 6 to 17 +/- 3 microM, whereas it had no effect on Vmax (4.2 +/- 0.2 nmol.mg-1.min-1). Based on complementary analysis by Dixon- and Cornish-Bowden-plots the following compounds were identified as competitive inhibitors of Na+-dependent taurocholate uptake: cholate (Ki = 140 +/- 30 microM); taurochenodeoxycholate (Ki = 9 +/- 3 microM); chenodeoxycholate (Ki = 53 +/- 6 microM); progesterone (Ki = 110 +/- 30 microM); 17-beta-estradiol-3-sulfate (Ki = 28 +/- 4 microM); bumetanide (Ki = 440 +/- 85 microns); furosemide (Ki = 460 +/- 140 microM); verapamil (Ki = 65 +/- 35 microM); and phalloidin (Ki = 850 +/- 350 microM). In contrast, noncompetitive inhibition was found with bromosulfophthalein (Ki = 12 +/- 2 microM), cyclosporin A (Ki = 3 +/- 1 microM) and 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (Ki = 45 +/- 7 microM). These results support the concept of multispecificity of the Na+-dependent basolateral bile acid uptake system with respect to different bile acids and drugs. In addition, the findings provide further evidence for bile acids and bromosulfophthalein being taken up into rat hepatocytes by different transport systems, thus supporting the assumption of multiple basolateral organic anion "carriers" with distinct, yet partially overlapping substrate specificities.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Williams and Wilkins
ISSN:0022-3565
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:37

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