The ability to transport solutes across epithelial membranes is vital for the function of many organs, e.g., secretion and reabsorption by the kidney. In turn, epithelial transport depends upon the coordinated function of individual transport systems located at opposite poles of the cells in the apical (BBM) and basolateral (BLM) membranes. Many of these membrane processes, particularly for anions, are not yet understood. Furthermore, because of their complex organization, functional importance, and exposed location, epithelial membranes are particularly susceptible to toxic effects of foreign chemicals. Our major recent emphasis has been on increasing our understanding of vectorial solute transport in polar epithelia, including the properties of specific carrier systems, the driving forces energizing transport, the regulation of transport events, and the coupling between events at opposite poles of the cells. Results for both organic (glucose, amino acids, organic acids) and inorganic (Na&, Cl minus, S04=) solutes emphasize the complexity of the chains of events which lead to active solute transport by epithelia and thus indicate that there are multiple sites for potential disruption by xenobiotics. Moreover, they also show that similar chains are responsible for transport of widely different solutes; thus, that the same mechanism may be responsible for breakdown in transport of unrelated solutes. For example, the organic cation, L-lysine, and the inorganic anion S04=, were shown to be transported via pH gradient-dependent mechanisms. Therefore, transport of both solutes could be markedly inhibited by the protonophore, pentachlorophenol, which collapses the pH gradient across the membrane.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES080031-09
Application #
4693292
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1985
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Srimaroeng, Chutima; Cecile, Jennifer Perry; Walden, Ramsey et al. (2013) Regulation of renal organic anion transporter 3 (SLC22A8) expression and function by the integrity of lipid raft domains and their associated cytoskeleton. Cell Physiol Biochem 31:565-78
Barros, Scott A; Srimaroeng, Chutima; Perry, Jennifer L et al. (2009) Activation of protein kinase Czeta increases OAT1 (SLC22A6)- and OAT3 (SLC22A8)-mediated transport. J Biol Chem 284:2672-9
Srimaroeng, C; Perry, J L; Pritchard, J B (2008) Physiology, structure, and regulation of the cloned organic anion transporters. Xenobiotica 38:889-935
Bow, Daniel A J; Perry, Jennifer L; Miller, David S et al. (2008) Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in freshly isolated rat hepatocytes. Drug Metab Dispos 36:198-202
Kimura, T; Perry, J; Anzai, N et al. (2007) Development and characterization of immobilized human organic anion transporter-based liquid chromatographic stationary phase: hOAT1 and hOAT2. J Chromatogr B Analyt Technol Biomed Life Sci 859:267-71
Aslamkhan, Amy G; Thompson, Deborah M; Perry, Jennifer L et al. (2006) The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3. Am J Physiol Regul Integr Comp Physiol 291:R1773-80
Bow, Daniel A J; Perry, Jennifer L; Simon, John D et al. (2006) The impact of plasma protein binding on the renal transport of organic anions. J Pharmacol Exp Ther 316:349-55
Perry, Jennifer L; Dembla-Rajpal, Neetu; Hall, Laura A et al. (2006) A three-dimensional model of human organic anion transporter 1: aromatic amino acids required for substrate transport. J Biol Chem 281:38071-9
Pritchard, John B; Miller, David S (2005) Expression systems for cloned xenobiotic transporters. Toxicol Appl Pharmacol 204:256-62
Bleasby, Kelly; Hall, Laura A; Perry, Jennifer L et al. (2005) Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). J Pharmacol Exp Ther 314:923-31

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