Effects of acid-base variables and the role of carbonic anhydrase on oxalate secretion by the mouse intestine in vitro

Jonathan M. Whittamore, Susan C. Frost, Marguerite Hatch

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Hyperoxaluria is a major risk factor for calcium oxalate kidney stones and the intestine is recognized as an important extra-renal pathway for eliminating oxalate. The membrane-bound chloride/bicarbonate (Cl-/HCO3-) exchangers are involved in the transcellular movement of oxalate, but little is understood about how they might be regulated. HCO3-, CO2, and pH are established modulators of intestinal NaCl cotransport, involving Na+/H+ and Cl-/HCO3- exchange, but their influence on oxalate transport is unknown. Measuring14C-oxalate and36Cl fluxes across isolated, short-circuited segments of the mouse distal ileum and distal colon we examined the role of these acid-base variables and carbonic anhydrase (CA) in oxalate and Cl- transport. In standard buffer both segments performed net oxalate secretion (and Cl- absorption), but only the colon, and the secretory JOxsm pathway were responsive to HCO3- and CO2. Ethoxzolamide abolished net oxalate secretion by the distal colon, and when used in tandem with an impermeant CA inhibitor, signaled an intracellular CA isozyme was required for secretion. There was a clear dependence on HCO3- =CO2 as their removal eliminated secretion, while at 42 mmol/L HCO3- JOxsm was also decreased and JOxnet eradicated. Independent of pH, raising PCO2 from 28 to 64 mmHg acutely stimulated net oxalate secretion 41%. In summary, oxalate secretion by the distal colon was dependent on HCO3-, CA and specifically modulated by CO2, whereas the ileum was remarkably unresponsive. These findings highlight the distinct segmental heterogeneity along the intestine, providing new insights into the oxalate transport mechanism and how it might be regulated.

Original languageEnglish (US)
Article numbere12282
JournalPhysiological Reports
Volume3
Issue number2
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Anion exchange
  • Bicarbonate
  • Chloride
  • CO
  • Colon
  • Ileum
  • pH

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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