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In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion
Published on: November 10, 2011
Drug uptake systems in liver and kidney
J E van Montfoort1, B Hagenbuch, G M M Groothuis
1Centre for Biomembranes and Lipid Enzymology, Department Membrane Enzymology, Faculty of Chemistry, University of Utrecht, The Netherlands. j.e.vanmontfoort@chem.uu.nl
Current Drug Metabolism
|May 29, 2003
Summary
Drug elimination routes depend on molecular properties and transporter proteins. Organic anion transporting polypeptides (Oatps/OATPs) and solute carrier family (SLC22A) transporters like organic cation transporters (OCTs) and organic anion transporters (OATs) are key in liver and kidney drug uptake.
Area of Science:
- Pharmacology
- Biochemistry
- Physiology
Background:
- The liver and kidneys are primary routes for drug and metabolite excretion.
- Drug properties like molecular weight, hydrophilicity, and protein binding influence elimination pathways.
- Uptake transporters in hepatocytes and renal tubular cells are critical for determining a compound's main elimination route.
Purpose of the Study:
- To review the tissue distribution, substrate specificity, transport mechanisms, and regulation of key drug uptake transporters.
- To elucidate the roles of the organic anion transporting polypeptide (Oatp/OATP) superfamily (SLC21A) and the SLC22A family (OCTs and OATs).
Main Methods:
- Literature review focusing on Oatp/OATP, OCT, and OAT transporter families.
- Analysis of transporter characteristics including tissue distribution, substrate specificity, and transport mechanisms.
Main Results:
- Oatps/OATPs facilitate hepatic uptake of large, amphipathic organic anions, organic cations, and uncharged substrates.
- OCTs and OATs mediate the uptake of smaller organic cations and anions in both liver and kidney.
- Transporter affinity and specificity significantly impact drug elimination routes.
Conclusions:
- Uptake transporters play a crucial role in determining whether drugs are eliminated via the hepatobiliary system or kidneys.
- Understanding these transporters is vital for predicting drug disposition and optimizing drug therapy.
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