Enteric oxalate secretion is not directly mediated by the human CFTR chloride channel.
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 35SO(4)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.
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, P.O. Box 100275, Gainesville, FL 32610-00275, USA. rfreel@ufl.edu
Robert W
RW
Freel
Marguerite
M
Hatch
D000818:Animals; D002713:Chlorine / Q000493:pharmacokinetics; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000378:metabolism / Q000502:physiology*; D010070:Oxalates / Q000378:metabolism*; D018075:RNA, Complementary / Q000494:pharmacology; D011868:Radioisotopes / Q000493:pharmacokinetics; D014545:Urinary Calculi / Q000378:metabolism* / Q000503:physiopathology; D014982:Xenopus laevis
C505032:CFTR protein, human; D010070:Oxalates; D018075:RNA, Complementary; D011868:Radioisotopes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002713:Chlorine; D000242:Cyclic AMP