edoc

Differential effects of microsomal enzyme-inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2

Rausch-Derra, L. C. and Hartley, D. P. and Meier, P. J. and Klaassen, C. D.. (2001) Differential effects of microsomal enzyme-inducing chemicals on the hepatic expression of rat organic anion transporters, OATP1 and OATP2. Hepatology, Vol. 33, No. 6. pp. 1469-1478.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A5261658

Downloads: Statistics Overview

Abstract

The organic anion transporting polypeptides, Oatp1 (Slc21a1) and Oatp2 (Slc21a5), mediate hepatic uptake of cardiac glycosides. Previously, we demonstrated that chemicals that increase cytochrome P450s differentially affect hepatic uptake of cardiac glycosides. We postulated that increased uptake of cardiac glycosides observed after pretreatment of animals with phenobarbital (PB) and pregnenolone-16alpha-carbonitrile (PCN) occurs via increased hepatic expression of Oatp1 and/or Oatp2. Male Sprague-Dawley rats were injected with PB, PCN, 3-methylcholanthrene (3-MC), or vehicle for 4 days. Branched-DNA (bDNA) signal amplification and Western blot analyses were used to assess hepatic Oatp1 and Oatp2 mRNA and protein, respectively. The expression of Oatp1 was not increased by any chemical treatment. Increases in Oatp2 expression were observed from livers of rats treated with PB and PCN, in which PCN caused a robust elevation of Oatp2 mRNA and protein. Oatp2 expression was suppressed in response to 3-MC. To determine the temporal effects of PCN treatment on the expression of Oatp2, rats were administered PCN, livers were extracted at various times, and Oatp2 expression was analyzed. Maximal expression of Oatp2 mRNA was observed at 24 hours and remained elevated, whereas the amount of Oatp2 protein increased throughout the 96-hour interval. The finding that Oatp2 expression increases in response to PB and PCN is consistent with our previous findings that PB and PCN enhance hepatic uptake of cardiac glycosides. These results suggest that Oatp2, but not Oatp1, is inducible by PB and PCN, which imparts the increased capacity of the liver to extract cardiac glycosides from the plasma.
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:Saunders
ISSN:0270-9139
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:37

Repository Staff Only: item control page