Abstract
To assess the importance of brain cytochrome P450 (P450) activity in mu opioid analgesic action, we generated a mutant mouse with brain neuron-specific reductions in P450 activity; these mice showed highly attenuated morphine antinociception compared with controls. Pharmacological inhibition of brain P450 arachidonate epoxygenases also blocked morphine antinociception in mice and rats. Our findings indicate that a neuronal P450 epoxygenase mediates the pain-relieving properties of morphine.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Analgesics, Opioid / administration & dosage
-
Analgesics, Opioid / pharmacology*
-
Animals
-
Brain / drug effects*
-
Brain / enzymology
-
Brain / metabolism
-
Cytochrome P-450 CYP2J2
-
Cytochrome P-450 Enzyme Inhibitors
-
Cytochrome P-450 Enzyme System / drug effects*
-
Cytochrome P-450 Enzyme System / genetics
-
Cytochrome P-450 Enzyme System / metabolism
-
Dose-Response Relationship, Drug
-
Enzyme Inhibitors / pharmacology
-
Female
-
Male
-
Mice
-
Mice, Transgenic
-
Morphine / administration & dosage
-
Morphine / pharmacology
-
Neural Pathways / drug effects
-
Neural Pathways / enzymology
-
Neural Pathways / metabolism
-
Neurons / drug effects*
-
Neurons / enzymology
-
Neurons / metabolism
-
Pain / drug therapy*
-
Pain / enzymology
-
Pain / metabolism
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, Opioid, mu / metabolism*
-
Signal Transduction
-
Time Factors
Substances
-
Analgesics, Opioid
-
Cytochrome P-450 Enzyme Inhibitors
-
Enzyme Inhibitors
-
Receptors, Opioid, mu
-
Morphine
-
Cytochrome P-450 Enzyme System
-
Cytochrome P-450 CYP2J2