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 microM), 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.
Arao
M
M
Department of Medicine, Kobe University School of Medicine, Japan.
Yamaguchi
T
T
Sugimoto
T
T
Fukase
M
M
Chihara
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001859:Bone Neoplasms; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates; D010879:Piperazines; D011506:Proteins; D005576:Colforsin; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium