Involvement of protein kinase C in the stimulation of sodium-dependent phosphate transport by parathyroid hormone in osteoblast-like cells

Department of Medicine, Kobe University School of Medicine, Japan.

The rat osteosarcoma cell line UMR-106 has an osteoblast-like phenotype and possesses parathyroid hormone (PTH)-responsive dual signal transduction systems [adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) and calcium-protein kinase C (Ca-PKC)]. These cells transport inorganic phosphate (Pi) by a Na(+)-dependent carrier under stimulation by PTH. The present study aimed to clarify PTH-responsive signal transduction mechanisms in the regulation of Na(+)-dependent Pi transport by PTH in UMR-106 cells. Exposure of these cells to 10(-7) mol/l PTH induced a significant increase in Pi uptake within 30 min of incubation and it became maximal after 2 h. Parathyroid hormone (10(-9)-10(-7) mol/l) stimulated Pi uptake dose dependently. Activation of PKC by 12-O-tetradecanoyl phorbol-13-acetate (TPA) also increased Pi uptake in time- and dose-dependent manners similar to PTH. In contrast, neither PKA activation by 10(-4) mol/l forskolin or by 10(-4) mol/l dibutyryladenosine 3',5'-cyclic monophosphate nor calcium ionophore treatment with 10(-7) mol/l A23187 or with 10(-7) mol/l ionomycin during 3-h incubations affect Pi uptake, except its increase by 10(-4) mol/l forskolin at a 3-h incubation. These agents had no influence on Pi uptake even in combined treatments with TPA. The PTH-induced increase in Pi uptake was abolished almost completely by pretreating cells with PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 mumol/l) or staurosporin (10 and 50 nmol/l), and by down-regulating PKC with a prolonged TPA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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