Enteric oxalate secretion is not directly mediated by the human CFTR chloride channel
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Abstract
The secretion of the oxalate anion by intestinal epithelia is a functionally significant component of oxalate homeostasis and hence a relevant factor in the etiology and management of calcium oxalate urolithiasis. To test the hypothesis that human cystic fibrosis transmembrane conductance regulator (hCFTR) can directly mediate the efflux of the oxalate anion, we compared cAMP-stimulated 36Cl−, 14C-oxalate, and 35SO4 2− efflux from Xenopus oocytes expressing hCFTR with water-injected control oocytes. hCFTR-expressing oocytes exhibited a large, reversible cAMP-dependent increase in whole cell conductance measured using a two-electrode voltage clamp and a 13-fold increase in rate of cAMP-stimulated 36Cl− efflux. In contrast, the rate constants of oxalate and sulfate efflux were low and unaffected by cAMP in either control or hCFTR-expressing oocytes. We conclude that the human CFTR gene product does not directly mediate oxalate efflux in secretory epithelia and hence is not directly involved in oxalate homeostasis in humans.
Keywords
Anion selectivity Excretion Renal stones Sulfate Xenopus oocyteNotes
Acknowledgments
Dr. David Dawson (Department of Physiology/Pharmacology, Oregon Health & Science University) kindly provided the wild-type hCFTR cDNA and Dr. M. Green (University of Florida) prepared the cRNA. Amanda Morris assisted in maintenance and surgical procedures. Supported by NIH DK060544 (RWF), DK056245 (MH), and the Oxalosis and Hyperoxaluria Foundation.
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