PROTEIN-KINASE-C IS CRUCIAL FOR THE STIMULATION OF SODIUM-DEPENDENT PHOSPHATE-TRANSPORT BY PARATHYROID HORMONE-RELATED PEPTIDE IN OSTEOBLAST-LIKE CELLS

In the present study, we investigated the role of parathyroid hormone-related peptide (PTHrP)-responsive dual signal transduction systems in the regulation of sodium-dependent phosphate (Pi) transport by PTHrP in UMR-106 cells. Exposure of the cells to 10(-7)M human (h) PTHrP-(1-34) induced a significant increase in Pi uptake within 15 min of incubation. The peptide stimulated Pi uptake dose-dependently at the range of 10(-11)-10(-7) M. Activation of protein kinase C (PKC) by 12-O-Tetradecanoyl phorbol-13-acetate (TPA) also increased Pi uptake in time- and dose-dependent manners similar to PTHrP. In contrast, neither activation of adenylate cyclase by 10(-5)M forskolin nor calcium ionophore treatment with 10(-7)M A23187 affect Pi uptake. These agents failed to influence on Pi uptake even in combined treatment with TPA. The PTHrP-induced increase in Pi uptake was strongly inhibited by pretreating cells with PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 muM), and by down-regulating PKC with a prolonged TPA pretreatment. These results indicate that the messenger system mediated by PKC, rather than adenylate cyclase or cytosolic calcium, plays a crucial role in the regulation of sodium-dependent Pi transport by PTHrP in the osteoblast-like cells. (C) 1994 Academic Press, Inc.