Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 105, Issue 4, Pages 353-360Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.FP0071287
Keywords
morphine; analgesia; individual difference; P-glycoprotein; blood-brain barrier
Categories
Ask authors/readers for more resources
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 or 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available