Okadaic acid enhances prostaglandin E1-induced alkaline phosphatase activity in osteoblast-like cells: regulation at a point downstream from protein kinase A.
We examined the effect of okadaic acid, an inhibitor of protein phosphatase type 1 and 2A, on prostaglandin E1 (PGE1)-induced alkaline phosphatase (ALP) activity in osteoblast-like MC3T3-E1 cells. PGE1 increased ALP activity dose dependently in the range between 10 nM and 0.3 microM in these cells. The pretreatment with okadaic acid enhanced the PGE1-induced ALP activity in a dose-dependent manner in the range between 0.1 and 5 nM. On the other hand, 1-norokadaone, a less potent analogue of okadaic acid, had no effect on the PGE1-induced ALP activity. Tautomycin, an another inhibitor of protein phosphatase type 1 and 2A, also enhanced the PGE1-induced ALP activity. PGE1 stimulated cAMP accumulation dose dependently in the range between 10 nM and 0.3 microM. However, PGE1 had no effect on the formation of inositol phosphates. Okadaic acid did not affect the PGE1-induced cAMP accumulation. Okadaic acid dose dependently enhanced the dibutyryl cAMP-induced ALP activity. These results strongly suggest that protein phosphatase type 1 and/or 2A act as a regulator of ALP activity at a point downstream from protein kinase A in osteoblast-like cells.
Ito
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Suzuki
A
A
Watanabe-Tomita
Y
Y
Oiso
Y
Y
Kozawa
O
O
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism*; D000527:Alprostadil / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D011714:Pyrans; D013141:Spiro Compounds
C084934:1-norokadaone; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D007295:Inositol Phosphates; D010080:Oxazoles; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; D019319:Okadaic Acid; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000469:Alkaline Phosphatase; D000527:Alprostadil