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1 Department of Biological Sciences, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan
2 Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
* To whom correspondence should be addressed. E-mail: shirose{at}bio.titech.ac.jp.
A new type of urea transporter was identified by a database search and shown to be highly expressed in the renal proximal tubule cells of teleosts; proximal tubule-type urea transporters have not been describe previously. We first identified urea transporterlike sequences in the fugu genome and in an EST database of rainbow trout. Based on these pieces of sequence information, we obtained a full-length cDNA for the eel ortholog, consisting of 378 amino acid residues, and named it "eUT-C". Although its sequence similarity to the known urea transporters is low (~35%), its heterologous expression in Xenopus oocytes indicated that it is a facilitative urea transporter sensitive to phloretin. Its activity is not dependent on Na+. Northern blot analysis showed that expression of eUT-C is highly restricted to the kidney, with weak expression in the stomach. In both tissues, eUT-C mRNA was strongly induced when eels were transferred from freshwater to seawater. Immunohistochemistry and in situ hybridization histochemistry revealed proximal tubule cell localization of eUT-C. Taking into account that (1) urea is mainly secreted from the gill where another type of urea transporter (eUT) has been identified and (2) fish excrete a very small volume of urine in seawater, we propose that eUT-C cloned here is a key component working in combination with the gill transporter to achieve an efficient urea excretory system in fish, namely eUT-C reabsorbs urea from glomerular filtrate and sends its to the gill, through circulation, for excretion.
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