Role of Phosphodiesterase 4 Isoenzyme in Alkaline Phosphatase Activation by Calcitonin in Porcine Kidney LLC-PK_1 Cells
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概要
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To confirm the intracellular signal transduction in regulation of alkaline phosphatase (ALP) activity by calcitonin in kidney tubular cells, effects of several inhibitors of cyclic nucleotide phosphodiesterase (PDE) isoenzymes and cyclic AMP-dependent protein kinase (PKA) on the action of salmon calcitonin in porcine kidney tubular epithelial cells LLC-PK1 were examined. A confluent culture of LLC-PK1 cells was treated with calcitonin and inhibitors in Dulbecco’s modified Eagle’s medium supplemented with 0.1% bovine serum albumin, and intracellular cyclic AMP content and ALP activity were measured after incubation for 30 min and 48 hr, respectively. Calcitonin and PDE 4 inhibitors increased cyclic AMP level and ALP activity in the cells, and PDE 4 inhibitors synergistically potentiated the effects of calcitonin. Calcitonin induced ALP activation by treatment for the first 1 hr, as well as continuous treatment for 48 hr, while it never increased the enzyme activity just after 1-hr exposure. Rolipram, an inhibitor of PDE 4 isoenzyme, induced ALP activation by itself and in combination with calcitonin by only a long term treatment (48 hr). The activation of ALP by calcitonin and rolipram each alone and in combination was completely abolished by a PKA inhibitor, H-89. These results confirm that calcitonin induces ALP activation through the cyclic AMP-PKA pathway and that PDE 4 isoenzyme is closely associated with the calcitonin-receptor system and plays a major role in hydrolysis of cyclic AMP produced in the kidney tubular cells.
- 社団法人 日本薬理学会の論文
著者
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TAKAGI Kenzo
Department of Medical Technology, Nagoya University School of Health Sciences
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Miyamoto Ken-ichi
金沢大学 薬学部臨床薬物情報
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Miyamoto Ken-ichi
Dep. Of Clinical Pharmacy Graduate School Of Natural Sci. And Technol. Kanazawa Univ.
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Miyamoto K
Kanazawa Univ Kanazawa
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YAMAMOTO Shinya
Division of Natural Science, Osaka Kyoiku University
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Suzuki R
Graduate School Of Pharmaceutical Sciences Nagoya City University
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Takagi K
Department Of Internal Medicine Nagoya University School Of Medicine
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HORITA Takashi
Department of Pharmacology, Faculty of Den tistry, Tokyo Medical and Dental University
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MIYAMOTO Ken-ichi
Division of Pharmacy and Health Sciences, Graduate School of Natural Science and Technology, Kanazaw
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SUZUKI Ryoji
Division of Pharmacy and Health Sciences, Graduate School of Natural Science and Technology, Kanazaw
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HORITA Takashi
Faculty of Pharmaceutical Sciences, Hokuriku University
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WAKI Yoshihiro
Division of Pharmacy and Health Sciences, Graduate School of Natural Science and Technology, Kanazaw
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Miyamoto K
Department Of Hospital Pharmacy School Of Medicine Kanazawa University
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Takagi Kenzo
Department Of Internal Medicine Nagoya University School Of Medicine
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Horita Takashi
Department Of Pharmacology Faculty Of Den Tistry Tokyo Medical And Dental University
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Waki Yoshihiro
Department Of Pharmacology And Pharmaceutics Graduate School Of Natural Science And Technology Kanaz
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Waki Yoshihiro
Department Of Pharmacology Hokuriku University School Of Pharmacy
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Suzuki R
Division Of Pharmacy And Health Sciences Graduate School Of Natural Science And Technology Kanazawa
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Miyamoto Ken'ichi
Hospital Pharmacy School Of Medicine Kanazawa University
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Yamamoto S
Department Of Pharmacology And Pharmaceutics Graduate School Of Natural Science And Technology Kanaz
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Yamamoto Shinya
Division Of Natural Science Osaka Kyoiku University
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Miyamoto Ken-ichi
Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University
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SUZUKI Ryoji
Department of Physics, Science University
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SUZUKI Ryoji
Department of Physics, Science University of Tokyo
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