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Regulation of Phosphate Uptake in Primary Cultured Rabbit Renal Proximal Tubule Cells by Glucocorticoids: Evidence for Nongenomic as Well as Genomic Mechanisms¹

Department of Veterinary Physiology (S.-H.P., H.-J.H.), College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju 500–757, Korea; and Biochemistry Department (M.T.), School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14214

Address all correspondence and requests for reprints to: Ho-Jae Han, Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Kwangju 500–757, Korea. E-mail: hjhan{at}chonnam.chonnam.ac.kr

We have investigated the nongenomic as well as the genomic effects of glucocorticoids on phosphate (Pi) uptake in primary rabbit renal proximal tubule cells (PTCs) and have defined the involved signaling pathways. In the present study, cortisol-BSA (cortisol-BSA) (>10^-9 M, 30 min) was found to inhibit Pi uptake in a time- and concentration-dependent manner. However, progesterone-BSA (P₄-BSA), 17ß-estradiol-BSA (E₂-BSA), testosterone-BSA (T₄-BSA), aldosterone, P₄, E₂, and T₄ (10^-9 M, 1 h) had no effect on Pi uptake. In addition, cortisol-BSA (10^-9 M) did not affect either Na⁺ uptake or -methylglucopyranoside (-MG) uptake. The cortisol-BSA-induced inhibition of Pi uptake was associated with a decrease in the V_max for Pi uptake, rather than the K_m. The inhibitory effect of cortisol-BSA was not blocked either by actinomycin D (an inhibitor of transcription), cycloheximide (an inhibitor of translation), or classical glucocorticoid receptor antagonists (RU 486 or P₄). The cortisol-BSA-induced inhibition of Pi uptake was blocked by two phospholipase C (PLC) inhibitors (neomycin or U73122), and two protein kinase C (PKC) inhibitors (staurosporine or bisindolylmaleimide I) but not by two adenylate cyclase/protein kinase A inhibitors [SQ 22536 (an adenylate cyclase inhibitor) or myristoylated protein kinase A inhibitor amide 14–22]. Furthermore, cortisol-BSA promoted the translocation of PKC from the cytosolic fraction to the membrane fraction, while having no effect on the activity of adenylate cyclase. Our observations may thus be interpreted as indicating that cortisol does indeed inhibit renal Pi uptake via a nongenomic mechanism, which involves the PLC/PKC pathway.

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