Submitted on February 12, 2003
Accepted on February 11, 2004
OKP cells express the Na dicarboxylate cotransporter NaDC-1
Seiji Aruga1, Ana Pajor2, Kiyoshi Nakamura1, Liping Liu1, Orson W Moe3, Patricia A Preisig1*, and Robert J Alpern1
1 Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
2 Physiology, University of Texas Medical Branch, Galveston, Texas, USA
3 Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Internal Medicine, Veteran's Administration Medical Center, Dallas, Texas, USA
* To whom correspondence should be addressed. E-mail: Patricia.Preisig{at}UTSouthwestern.edu.
Urinary citrate concentration, a major determinant in the formation of kidney stones, is primarily determined by its rate of reabsorption in the proximal tubule. Citrate reabsorption is mediated by the Na-dicarboxylate cotransporter, NaDC-1. The opossum kidney (OKP) cell line possesses many characteristics of the renal proximal tubule. The OKP NaDC-1 cDNA (oNaDC-1) was cloned and encodes a 2.4 kb mRNA. When injected into Xenopus oocytes, the cotransporter is expressed and demonstrates Na-coupled citrate transport with a stoichiometry of 
3 Na:1 citrate, specificity for di- and tricarboxylates, pH-dependent citrate transport, and pH-independent succinate transport, all characteristics of the other NaDC-1 orthologs. Chronic metabolic acidosis increases proximal tubule citrate reabsorption, leading to profound hypocitraturia and an increased risk for stone formation. Under the conditions studied, endogenous OKP NaDC-1 mRNA abundance is not regulated by changes in media pH. However, in OKP cells transfected with a GFP-oNaDC-1 construct, media acidification increases Na-dependent citrate uptake, demonstrating post-transcriptional acid regulation of NaDC-1 activity.
