Abstract
In this study we investigated the effect of cannabinoids on [3H]glutamate release from hippocampal synaptosomes of rat and CB1-null mutant mouse. In the rat, cannabinoid receptor agonists, i.e. CP55,940 (EC50, 0.84 microm), WIN55,212-2 (EC50, 3.47 microm), ACEA (EC50, 17.8 microm), and R-(+)-methanandamide (EC50, 19.8 microm) concentration-dependently inhibited the 25-mm-K+ depolarization-evoked release of [3H]glutamate and, among them, WIN55,212-2 displayed the greatest efficacy. The CB1 receptor antagonists SR141716A (1-5 microm) and AM251 (1 microm) and the VR1 vanilloid receptor antagonist capsazepine (10 microm) did not antagonize the effect of the agonists. SR141716A by itself attenuated the evoked [3H]glutamate release. WIN55,212-2 inhibited the release of [3H]glutamate in CB1 -/- mice as well. These data demonstrate that the action of cannabinoids on glutamate release in the hippocampus is pharmacologically distinct and independent from the cloned CB1 receptor.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / pharmacology
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Animals
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Arachidonic Acids / pharmacology
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Benzoxazines
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Cannabinoids / pharmacology*
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Capsaicin / analogs & derivatives*
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Capsaicin / pharmacology
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Chromatography, High Pressure Liquid
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Cyclohexanols / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Glutamic Acid / metabolism*
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Hippocampus / cytology
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Hippocampus / drug effects*
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Hippocampus / metabolism
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Male
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Morpholines / pharmacology
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Naphthalenes / pharmacology
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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Radioactivity
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Rats
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Rats, Wistar
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Receptor, Cannabinoid, CB1 / metabolism*
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Rimonabant
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Synaptosomes / drug effects*
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Synaptosomes / metabolism
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Tritium / metabolism
Substances
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Analgesics
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Arachidonic Acids
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Benzoxazines
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Cannabinoids
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Cyclohexanols
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Morpholines
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Naphthalenes
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Piperidines
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Pyrazoles
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Receptor, Cannabinoid, CB1
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arachidonyl-2-chloroethylamide
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Tritium
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methanandamide
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AM 251
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Glutamic Acid
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
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capsazepine
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Rimonabant
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Capsaicin