Dexamethasone and Cyclic AMP Regulate Sodium Phosphate Cotransporter (NaPi-IIb and Pit-1) mRNA and Phosphate Uptake in Rat Alveolar Type II Epithelial Cells

Alveolar epithelial type II (AT II) cells need phosphate (Pi) for surfactant synthesis. The Na-dependent (Nad) Pi transporters NaPi-IIb and Pit-1 are expressed in lung, but their expression, regulation, and function in AT II cells remain unclear. We studied NaPi-IIb and Pit-1 mRNA expression in cultured AT II cells isolated from adult rat lung, their regulation by agents known to enhance surfactant production, dexamethasone (dex) and dibutyryl cyclic AMP (cAMP), and the effects of dex and cAMP on Nad Pi uptake by this cell type. By Northern analysis, cultured AT II cells expressed both NaPi-IIb (4.8 and 4.0kb) and Pit-1 (4.3kb) mRNA. Treatment with 100nmol/l dex for 24h decreased the expression of both mRNAs (to 0.48±0.06 and 0.77±0.05, respectively, as compared to control), while 0.1mmol/l cAMP stimulated NaPi-IIb (1.94±0.22) but not Pit-1 mRNA (0.90±0.05, compared to vehicle-treated cells). NaPi-IIb and Pit-1 proteins could not be identified by western analysis of plasma membrane preparations of cultured AT II cells. AT II cells take up Pi in a Nad manner. Uptake was slightly (to 0.78-fold of the control) decreased by 100nmol/l dex but not affected by 0.1mmol/l cAMP treatment. Although NaPi-IIb mRNA expression was maintained to some extent by AT II cells kept in primary culture, Pi uptake was more closely related to Pit-1 mRNA expressio