Linked Life Data

19237515

Source:http://linkedlifedata.com/resource/pubmed/id/19237515

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pubmed-article:19237515pubmed:abstractTextStatins are widely used to treat dyslipidemia. Effects of statins in addition to low-density lipoprotein lowering include altered platelet aggregation, requiring drug uptake into platelets. Possible candidates for mediating intraplatelet accumulation of statins include members of the organic anion-transporting polypeptide family such as OATP2B1 (SLCO2B1), a high-affinity uptake transporter for atorvastatin. Therefore, we analyzed OATP expression, localization, and function in human platelets. OATP2B1, but not OATP1B1, was detected in platelets and megakaryocytes on transcript and protein levels. Protein localization was almost exclusively confined to the plasma membrane. Moreover, we could demonstrate significant inhibition of estrone sulfate uptake into platelets by atorvastatin as well as direct transport of atorvastatin into platelets using a liquid chromatography-tandem mass spectrometry method. As a consequence of OATP2B1-mediated uptake of atorvastatin, we observed significant atorvastatin-mediated reduction of thrombin-induced Ca(2+) mobilization in platelets (37.3 +/- 6.7% of control at 15 microM atorvastatin), mechanistically explainable by reduced lipid modification of signal proteins. This effect was reversed by addition of mevalonate. Finally, we demonstrated expression of HMG-CoA reductase, the primary target of atorvastatin, in platelet cytosol. In conclusion, OATP2B1 is an uptake transporter expressed in platelets and is involved in statin-mediated alteration of platelet aggregation.lld:pubmed
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pubmed-article:19237515pubmed:articleTitleHuman platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin.lld:pubmed
pubmed-article:19237515pubmed:affiliationDepartment of Pharmacology, Research Center of Pharmacology and Experimental Therapeutics, Ernst-Moritz-Arndt-University, Friedrich-Loeffler-Str. 23 D, D-17487 Greifswald, Germany.lld:pubmed
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