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

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(−)/[Image: see text]) exchangers are involved in the transcellular movement of oxalate, but...

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Detalles Bibliográficos
Autores principales: Whittamore, Jonathan M, Frost, Susan C, Hatch, Marguerite
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393191/
https://www.ncbi.nlm.nih.gov/pubmed/25716924
http://dx.doi.org/10.14814/phy2.12282
Descripción
Sumario: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(−)/[Image: see text]) exchangers are involved in the transcellular movement of oxalate, but little is understood about how they might be regulated. [Image: see text], CO(2), and pH are established modulators of intestinal NaCl cotransport, involving Na(+)/H(+) and Cl(−)/[Image: see text] exchange, but their influence on oxalate transport is unknown. Measuring (14)C-oxalate and (36)Cl 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 [Image: see text] pathway were responsive to [Image: see text] and CO(2). 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 [Image: see text] as their removal eliminated secretion, while at 42 mmol/L [Image: see text] [Image: see text] was also decreased and [Image: see text] eradicated. Independent of pH, raising Pco(2) from 28 to 64 mmHg acutely stimulated net oxalate secretion 41%. In summary, oxalate secretion by the distal colon was dependent on [Image: see text], CA and specifically modulated by CO(2), 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.