PS 10-06 ALDOSTERONE MODULATES EXPRESSION OF AN ACID-SECRETING AMMONIA TRANSPORTER Rhcg IN INTERCALATED CELLS OF THE COLLECTING DUCTS

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Abstract

Objective:

Main adverse effects of renin-angiotensin-aldosterone system (RAAS) blockers are metabolic acidosis and hyperkalemia, which limit the use of RAAS blockers for treatment of patients with chronic kidney disease. The mechanism of urinary acid secretion by the RAAS has not been fully understood. Rhesus blood group C glycoprotein (Rhcg) is an ammonia transporter which cooperates with H+-ATPase to secrete H+ from the intercalated cells of the collecting duct in the kidney. We hypothesize that aldosterone increases acid secretion by regulating Rhcg.

Design and Method:

In the present study, effects of aldosterone on the regulation of Rhcg were examined in vivo and in vitro. Mice were continuously administered aldosterone (40 μg/body/day) or vehicle for a week. Urinary pH, ammonia excretion, and titratable acids were measured. Membrane fraction of the whole kidney was extracted. IN-IC cells (a rat intercalated cell line) were treated with aldosterone (10–6 M) for 24 h, and then mRNA, whole cell protein, and membrane fraction were extracted. The Rhcg mRNA and protein expressions were measured by real-time PCR and Western blotting, respectively. The expression of serum and glucocorticoid-regulated kinase 1 (Sgk1) mRNA was also measured in IN-IC cells.

Results:

Administration of aldosterone increased ammonia in urine and Rhcg protein expression in membrane fraction of the whole kidney by 90%, respectively. In IN-IC cells, treatment with aldosterone increased expressions of Rhcg protein in membrane fraction by 220% and Sgk1 mRNA by 200%, respectively. Similarly to the endogenous Rhcg expression, aldosterone increased the expression of Flag-tagged mice Rhcg in membrane fraction.

Conclusions:

These results suggest that RAAS blockers cause metabolic acidosis, in part, by inhibiting the effect of aldosterone on membrane distribution of Rhcg in the intercalated cells of the collecting ducts.

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