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Pendrin

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• Soleimani
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• Wagner
• Wall
• Xing, Sidransky
• Yoshino

Soleimani

Regulation of the apical Cl-/HCO-3 exchanger pendrin in rat cortical collecting duct in metabolic acidosis.

Petrovic S, Wang Z, Ma L, Soleimani M.

Am J Physiol Renal Physiol. 2003 Jan;284(1):F103-12. Epub 2002 Aug 13.

"Pendrin is an apical Cl(-)/OH(-)/HCO(3)(-) exchanger in beta-intercalated cells (beta-ICs) of rat and mouse cortical collecting duct (CCD). However, little is known about its regulation in acid-base disorders. Here, we examined the regulation of pendrin in metabolic acidosis, a condition known to decrease HCO(3)(-) secretion in CCD. Rats were subjected to NH(4)Cl loading for 4 days, which resulted in metabolic acidosis. Apical Cl(-)/HCO(3)(-) exchanger activity in beta-ICs was determined as amplitude and rate of intracellular pH change when Cl was removed in isolated, microperfused CCDs. Intracellular pH was measured by single-cell digital ratiometric imaging using fluorescent pH-sensitive dye 2',7'-bis-(3-carboxypropyl)-5-(and-6)-carboxyfluorescein-AM. Pendrin mRNA expression in kidney cortex was examined by Northern blot hybridizations. Expression of pendrin protein was assessed by indirect immunofluorescence. Microperfused CCDs isolated from acidotic rats demonstrated approximately 60% reduction in apical Cl(-)/HCO(3)(-) exchanger activity in beta-ICs (P < 0.001 vs. control). Northern blot hybridizations indicated that the mRNA expression of pendrin in kidney cortex decreased by 68% in acidotic animals (P < 0.02 vs. control). Immunofluorescence labeling demonstrated significant reduction in pendrin expression in CCDs of acidotic rats. We conclude that metabolic acidosis decreases the activity of the apical Cl(-)/HCO(3)(-) exchanger in beta-ICs of the rat CCD by reducing the expression of pendrin. Adaptive downregulation of pendrin in metabolic acidosis indicates the important role of this exchanger in acid-base regulation in the CCD."

Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex.

Soleimani M, Greeley T, Petrovic S, Wang Z, Amlal H, Kopp P, Burnham CE.

Am J Physiol Renal Physiol. 2001 Feb;280(2):F356-64.

"The identities of the apical Cl-/base exchangers in kidney proximal tubule and cortical collecting duct (CCD) cells remain unknown. Pendrin (PDS), which is expressed at high levels in the thyroid and its mutation causes Pendred's syndrome, is shown to be an anion exchanger. We investigated the renal distribution of PDS and its function. Our results demonstrate that pendrin mRNA expression in the rat kidney is abundant and limited to the cortex. Proximal tubule suspensions isolated from kidney cortex were highly enriched in pendrin mRNA. Immunoblot analysis studies localized pendrin to cortical brush-border membranes. Nephron segment RT-PCR localized pendrin mRNA to proximal tubule and CCD. Expression studies in HEK-293 cells demonstrated that pendrin functions in the Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange modes. The conclusion is that pendrin is an apical Cl-/base exchanger in the kidney proximal tubule and CCD and mediates Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange."
 

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