Regulation of AQP6 mRNA and protein expression in rats in response to altered acid-base or water balance

In the rat, aquaporin-6 (AQP6) is mainly localized in intercalated cells (I Cs) in collecting ducts, where it is exclusively associated with intracellu lar vesicles. In this study, we examined whether AQP6 protein and mRNA expr ession were regulated in the inner medulla or inner stripe of the outer med ulla. Rats treated with dietary alkali or acid load for 7 days with a fixed daily water intake revealed appropriate changes in urine pH but unchanged urine output. AQP6 protein and mRNA abundance were increased in alkali-load ed rats (187 +/- 18 and 151 +/- 17% of control, respectively), whereas no c hanges were observed in acid-loaded rats. Immunohistochemistry revealed inc reased IC AQP6 labeling in alkali-loaded rats but not in acid-loaded rats. In contrast, administration of NH4Cl in the drinking water for 2 wk (free a ccess to water) revealed a significant increase in AQP6 protein abundance ( 194 +/- 9% of control), but this was associated with increased water intake . Combined, this suggests that AQP6 expression was not affected by acid loa ding per se but rather was in response to changes in water intake. Consiste nt with this, water loading for 48 h was associated with increased AQP6 pro tein abundance, compared with thirsted rats. Moreover, rats with lithium-in duced nephrogenic diabetes insipidus had a threefold increase in both AQP6 protein and mRNA expression. Overall, these results suggest that AQP6 expre ssion in collecting duct ICs is regulated by altered acid/alkali load or wa ter balance. Thus AQP6 may contribute to maintenance of acid-base homeostas is and water balance.