Organic anion transporting polypeptides (OATPs): regulation of expression and function.
Martin Svoboda1, Juliane Riha, Katrin Wlcek
1Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Austria.
Current Drug Metabolism
|March 15, 2011
Summary
Human organic anion transporters (OATPs) move substances across cell membranes. Their altered expression in cancer and disease can affect drug toxicity and requires further study for therapeutic applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- The human organic anion transporter (OATP) family comprises eleven members involved in transporting diverse endogenous and exogenous compounds.
- OATPs are 12-transmembrane glycoproteins with conserved structural features, facilitating substrate translocation via a proposed rocker-switch mechanism.
- While some OATPs exhibit tissue-specific expression (e.g., OATP1B1/OATP1B3 in the liver), their distribution is altered in pathological conditions like cancer.
Purpose of the Study:
- To investigate the regulation and function of human organic anion transporters (OATPs).
- To understand how OATP expression changes in pathological conditions and its impact on substrate transport.
- To explore the therapeutic implications of OATP knowledge.
Main Methods:
- Analysis of OATP structure and function, including proposed transport mechanisms.
- Examination of OATP expression patterns in various tissues and in cancer.
- Investigation of regulatory mechanisms, including cytokines, nuclear receptors, epigenetic factors, and post-translational modifications.
- Studies using cell lines and animal models to elucidate OATP regulation and function.
Main Results:
- OATPs facilitate the transport of a wide range of molecules, including drugs, bile acids, and hormones.
- OATP expression patterns are disrupted in malignant tissues, with certain OATPs becoming upregulated.
- OATP expression is dynamically regulated by various factors, including cytokines and nuclear receptors.
- Altered OATP expression in disease affects substrate accumulation in excretory organs and blood/organ barriers.
Conclusions:
- Changes in OATP expression under pathological conditions significantly impact cellular accumulation of OATP substrates.
- Dysregulated OATP function can lead to increased drug toxicity and adverse drug reactions.
- Further research into OATP regulation and function is crucial for developing effective therapeutic strategies.
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