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Localization of the sulfate/anion exchanger in the rat liver

Fabio Quondamatteo,¹ Wolfgang Krick,² Yohannes Hagos,² Marie-Helen Krüger,¹ Katrin Neubauer-Saile,³ Rainer Herken,^1, Giuliano Ramadori,³ Gerhard Burckhardt,² and Birgitta C. Burckhardt²

¹Abteilung Histologie, ²Abteilung Vegetative Physiologie und Pathophysiologie, and ³Abteilung Gastroenterologie und Endokrinologie, Georg August Universität Göttingen, Göttingen, Germany

Submitted 20 October 2005 ; accepted in final form 9 December 2005

ABSTRACT

Although the sulfate/anion transporter (sat-1; SLC26A1) was isolated from a rat liver cDNA library by expression cloning, localization of sat-1 within the liver and its contribution to the transport of sulfate and organo sulfates have remained unresolved. In situ hybridization and immunohistochemical studies were undertaken to demonstrate the localization of sat-1 in liver tissue. RT-PCR studies on isolated hepatocytes and liver endothelial and stellate cells in culture were performed to test for the presence of sat-1 in these cells. In sulfate uptake and efflux experiments, the substrate specificity of sat-1 was evaluated. Sat-1 mRNA was found in hepatocytes and endothelial cells. Sat-1 protein was localized in sinusoidal membranes and along the borders of hepatocytes. The canalicular region and bile capillaries were not stained. Sulfate uptake was only slightly affected by sulfamoyl diuretics or organo sulfates. Sulfate efflux from sat-1-expressing oocytes was enhanced in the presence of bicarbonate, indicating sulfate/bicarbonate exchange. Estrone sulfate was not transported by sat-1. Sat-1 may be responsible for the uptake of inorganic sulfate from the blood into hepatocytes to enable sulfation reactions. In hepatocytes and endothelial cells, sat-1 may also supply sulfate for proteoglycan synthesis.

endothelial cells; estrone sulfate; dehydroepiandrosterone sulfate; hepatocytes; sinusoidal localization; sulfate/bicarbonate exchange

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