The role of citrate in the kidney is two fold: it is a major renal metabolite supplying about 10% of the metabolic needs of the kidney, and citrate is a potent inhibitor of calcium nephrolithiasis. In urine, citrate maintains calcium in a soluble form by complexation thus preventing further growth to stones. The level of urinary citrate is determined by the extent of citrate reabsorption by the apical membrane of the proximal tubule. Citrate reabsorption has been attributed to NaDC-1, the first cloned dicarboxylate transporter from a growing family of dicarboxylate and sulfate transporters. Citrate is mainly trivalent at physiologic pH; but the divalent form is predominantly transported at the apical membrane. Thus citrate uptake at the apical membrane of the proximal tubule is pH sensitive No cell culture models have been available to explore the regulation of citrate transport in a native environment. The present studies utilizing OK cells, provide the first well characterized cell culture model of citrate transport. Many characteristics of citrate transport found in vivo are mimicked by OK cells. For example, citrate uptake increased by subjecting OK cells to acute and chronic acid loads as well as potassium depletion. This effect of acid-base status in OK cells is similar to that found in rats and humans and thus provides a model to study molecular regulation of citrate transport. Although citrate transport in OK cells corresponds to many aspects of citrate transport in vivo, other characteristics suggest that the transporter is not NaDC-1 Unexpectedly, the presence of apical calcium was found to regulate citrate transport, an effect not previously shown at the cellular level. OK cells studied in low calcium solutions demonstrated increased dicarboxylate citrate transport. A further increase in citrate uptake occurred with decreasing levels of magnesium after calcium removal. OK cells grown on permeable supports showed that the effect of calcium in regulating citrate transport occurs predominantly on the apical membrane. Extracellular calcium appears to change the magnitude of citrate transport as well as some intrinsic characteristics In summary these studies suggest that the apical membrane of the proximal tubule expresses a high affinity, calcium sensitive, sodium dependent dicarboxylate cotransporter which regulates urinary citrate excretion / acase@tulane.edu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_25808 |
| Date | January 2004 |
| Contributors | Hering-Smith, Kathleen S (Author), Navar, L. Gabriel (Thesis advisor) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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