Stimulatory and Inhibitory Effects of Forskolin on Adenylate Cyclase in Rat Normal Hepatocytes and Hepatoma Cells

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概要

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• Forskolin synergistically potentiated adenosine 3', 5'-cyclic monophosphate formation by prostaglandin E_1 (PGE_1) in rat normal hepatocytes freshly prepared by collagenase digestion and rat ascites hepatoma AH66 cells, but dose-dependently inhibited the accumulation by PGE_1 in AH66F cells. Forskolin activated adenylate cyclase in a dose-dependent manner in homogenates of all cell lines. In normal hepatocytes and AH66 cells, simultaneous addition of forskolin and other adenylate cyclase activators [isoproterenol (IPN), PGE_1,guanosine 5'-triphosphate sodium salt (GTP), 5'-guanylylimido-diphosphate sodium salt (Gpp (NH)p), NaF, cholera toxin, islet activating protein and MnCl_2] gave greater than additive responses. On the other hand, in AH66F cells, the effect of forskolin on adenylate cyclase was hardly influenced by GTP, but forskolin diminished the activities induced by high concentrations of GTP to that by the diterpene alone. Forskolin also significantly inhibited the PGE_1-stimulated and the guanine nucleotide binding regulatory protein-stimulated activities. Because AH66F cells were insensitive to IPN, the combination with forskolin and IPN gave similar activity to that obtained with the diterpene alone. The effect of forskolin on the activation by manganese ion was neither synergistic nor inhibitory but was additive in AH66F cells. These results suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide binding regulatory protein and the catalytic unit in normal hepatocytes and AH66 cells, but in AH66F cells forskolin interferes with the coupling of the two components of adenylate cyclase.

• 公益社団法人日本薬学会の論文

著者

• Takagi K

  Department Of Medical Technology Nagoya University School Of Health Sciences

• Kondo Takaaki

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• HASEGAWA Takaaki

  Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine

• Sanae F

  Hokuriku Univ. Kanazawa Jpn

• Sanae Fujiko

  Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar

• Sanae Fujiko

  Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku University

• Sanae Fujiko

  Department Of Applied Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Satake Tatsuo

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• Takagi Kenzo

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• MIYAMOTO Kenichi

  Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University

• Kawaguchi Takeshi

  Kyoto University Center For Student Health

• Matsunaga Takayuki

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• Hasegawa Takaaki

  Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine

• Hasegawa Takaaki

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• Koshiura Ryozo

  Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar

• MIYAMOTO Kenichi

  Third Division of the Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku

• Miyamoto K

  Department Of Medical Informatics Graduate School Of Medical Science Kanazawa University

• Koshiura R

  Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar

• Miyamoto K

  Department Of Engineering Physics And Mechanics Kyoto University

• MIYAMOTO Kenichi

  Department of Engineering Physics and Mechanics, Kyoto University

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