Increment of Activated Serine/Threonine Protein Phosphatase in Brain Membrane Fraction Synchronized with Antinociceptive Effect of Morphine in Mice
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概要
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We have examined the involvement of serine/threonine protein phosphatase (PP) sensitive to okadaic acid (OA) in the antinociceptive effect of morphine in mice. The present study was performed to elucidate subcellular distribution and activity of OA-sensitive PPs in the brain when mice exposed to morphine. Subcutaneous administration of morphine (5 mg/kg) produced the antinociceptive effect with the maximum 30 min after its administration, evaluated by tail-pinch test. The antinociception was accompanied by an increment of activity in OA-sensitive PPs in the membrane fraction prepared from the whole brain of mice treated with morphine: The temporal profile of the morphine-induced increment of OA-sensitive PP activity was consistent with that of antinociceptive effects of morphine. The morphine-induced increase in OA-sensitive PP activity was dependent on the dose and attenuated by the concurrent administration of naloxone (1 mg/kg). To identify the subtype of OA-sensitive PPs in morphine-enhanced activity, we examined the level of PP2A and PP5, OA-sensitive PPs, in the subcellular fraction prepared from the whole brain of mice receiving morphine. Western blot revealed that morphine elicited the significant increase in the level of PP5, but not PP2A, in the membrane fraction, with the same peak time for the increment of PP5 as the antinociception. No significant change was observed in the level of OA-sensitive PPs in the cytosolic fraction at any examined time after morphine. These results suggest that the translocation of PP5 to the membrane fraction is, at least in part, involved in the antinociceptive effect of morphine in mice.
著者
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Maeda Takehiko
Department of Pharmacology, Wakayama Medical University
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Kiguchi Norikazu
Department of Pharmacology, Wakayama Medical University
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Kobayashi Yuka
Department of Pharmacology, Wakayama Medical University
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Ozaki Masanobu
Department of Toxicology, Niigata University of Pharmacy and Applied Life Science
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Kishioka Shiroh
Department of Pharmacology, Wakayama Medical University
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Ozaki Masanobu
Department Of Cardiology Fukuoka University School Of Medicine
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Maeda Takehiko
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Kobayashi Yuka
Department Of Cardiology And Internal Medicine Yamashiro Public Hospital
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Kishioka Shiroh
Department Of Pharmacology Wakayama Medical College
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Kobayashi Yuka
Department Of Biological And Environmental Chemistry Faculty Of Agriculture Tottori University
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Kiguchi Norikazu
Department of Pharmacology, Faculty of Medicine, Wakayama Medical University, Japan
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- Increment of Activated Serine/Threonine Protein Phosphatase in Brain Membrane Fraction Synchronized with Antinociceptive Effect of Morphine in Mice
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