Negative Relationship Between Morphine Analgesia and P-Glycoprotein Expression Levels in the Brain
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概要
- 論文の詳細を見る
It is known that opioid analgesics given systemically have limited distribution into the brain because of their interaction with P-glycoprotein (P-gp), an ATP-dependent efflux pump acting at the blood-brain barrier (BBB). We previously found that morphine and fentanyl showed higher analgesic potencies in P-gp–deficient mice compared with those in wild-type mice, suggesting that their analgesic effects are considerably dependent on P-gp expression. In this study, we focused on individual differences in the analgesic effectiveness of morphine, in cortical P-gp expression, and in basal P-gp ATPase activity in male ICR mice. We found that there were 3- to 10-fold differences between the magnitude of morphine analgesia (3 mg/kg, s.c.; tail-pinch method) in mice. Furthermore, there was a significant negative correlation between morphine’s analgesic effects and individual P-gp expression in the cortex as estimated by western blot analysis. In addition, basal P-gp ATPase activities in isolated membrane preparations of brain capillary endothelial cells (BCECs) were negatively correlated with the magnitude of the analgesic effect of morphine. These results indicate that the individual differences in morphine analgesia may be due to some functional or quantitative differences in individual P-gp in BCECs, acting at the BBB.
- 社団法人 日本薬理学会の論文
- 2007-12-20
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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Tokuyama Shogo
Department Of Clinical Pharmacy Kobe Gakuin University Faculty Of Pharmaceutical Sciences
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Hamabe Wakako
Department Of Pharmacology Wakayama Medical University
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Hamabe Wakako
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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YAMAMOTO Chizuko
Department of Pharmacology, Wakayama Medical University
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Maeda Takehiko
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Kishioka Shiroh
Department Of Pharmacology Wakayama Medical College
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Yamamoto Chizuko
Department Of Pharmacology Wakayama Medical University
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Kiguchi Norikazu
Department of Pharmacology, Faculty of Medicine, Wakayama Medical University, Japan
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