Okadaic acid enhances prostaglandin E1-induced alkaline phosphatase activity in osteoblast-like cells: regulation at a point downstream from protein kinase A. 1996

Y Ito, and A Suzuki, and Y Watanabe-Tomita, and Y Oiso, and O Kozawa
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.

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.

UI MeSH Term Description Entries
D007295 Inositol Phosphates Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID. Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D010006 Osteoblasts Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone. Osteoblast
D010080 Oxazoles Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions. Oxazole,1,3-Oxazolium-5-Oxides,Munchnones,1,3 Oxazolium 5 Oxides
D011714 Pyrans Pyran
D003994 Bucladesine A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed) Dibutyryl Adenosine-3',5'-Monophosphate,Dibutyryl Cyclic AMP,(But)(2) cAMP,Bucladesine, Barium (1:1) Salt,Bucladesine, Disodium Salt,Bucladesine, Monosodium Salt,Bucladesine, Sodium Salt,DBcAMP,Dibutyryl Adenosine 3,5 Monophosphate,N',O'-Dibutyryl-cAMP,N(6),0(2')-Dibutyryl Cyclic AMP,AMP, Dibutyryl Cyclic,Adenosine-3',5'-Monophosphate, Dibutyryl,Cyclic AMP, Dibutyryl,Dibutyryl Adenosine 3',5' Monophosphate,Disodium Salt Bucladesine,Monosodium Salt Bucladesine,N',O' Dibutyryl cAMP,Sodium Salt Bucladesine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004988 Ethers, Cyclic Compounds of the general formula R-O-R arranged in a ring or crown formation. Cyclic Ether,Cyclic Ethers,Ether, Cyclic
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000469 Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.

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