Pendrins Function in the Kidney

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Intercalated cells are located in the distal nephron of man and rodents, representing a minority cell type that appears to be important for acid-base balance. Three types of intercalated cells have been identified, type A, type B and non-A/non-B. The major differences between these cell types relates to the expression and sub-cellular localization of several specific ion channels [see 46 for a recent comprehensive review]. Type A intercalated cell excrete protons through the apical H+-ATPase. Disruption of this channel results in a net decrease in H+ secretion. Type B intercalated cells express pendrin, which acts as a HCO~/Cl~ exchanger, on their apical membrane [25, 47]. Disruption of this channel results in decreased bicarbonate secretion and a tendency toward metabolic alkylosis [47]. In the mouse kidney, pendrin expression is regulated and can be modified by changes in acid-base status [48].

Mice deficient in pendrin (slc26a4~'~) have normal pH, renal function and fluid balance under non-stimulated conditions. However, during NaCl restriction, slc26a4_/~ mice have elevated urinary volume and Cl" excretion and develop metabolic alkylosis, volume depletion and relative hypotension [49]. Stimulation with the aldosterone analogue diozycorticosterone pivalate (DOCP) results in weight gain and hypertension in normal mice, but not in scl26a4_/~ mice [50]. These findings suggest that pendrin may play a role in the pathogenesis of mineralocorticoid-mediated hypertension.

To date, no fluid or electrolyte abnormality has been reported in patients with Pendred syndrome, although rigorous studies have yet to be reported, and it seems likely that subtle abnormalities will be found under certain stress conditions. Common polymorphisms have been found in PDS, including at least 2 non-synonymous coding variants. It is possible that these or other genetic variants in this gene affect the genetic risk of developing fluid and electrolyte imbalances or hypertension. Large-scale association studies are needed to establish or to refute this potential association between pendrin and the commonly seen essential hypertension.

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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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