Abstract
Cerebellar granule cells (CGCs) express the CB(1) subtype of cannabinoid receptor. CB(1) receptor agonists Win 55212-2, CP55940 and HU210 inhibit KCl-induced activation of nitric oxide synthase (NOS) in CGCs. Win 55212-2 has no effect on either basal NOS activity or on activation by N-methyl-D-aspartate and its effect is abolished by pre-treatment of the cells with pertussis toxin. The CB(1) receptor antagonist/inverse agonist SR141716A both reverses the effects of Win 55212-2 and produces an increase in NOS activity that is additive with KCl. These results support the hypothesis that activation of the CB(1) receptor in CGCs results in a decreased influx of calcium in response to membrane depolarization, resulting in a decreased activation of neuronal NOS.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Benzoxazines
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Calcium Channel Blockers / pharmacology
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / drug effects
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Cerebellum / enzymology*
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Cerebellum / metabolism
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Drug Interactions
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Female
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Male
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Morpholines / pharmacology
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Naphthalenes / pharmacology
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Nitric Oxide Synthase / metabolism*
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Nitric Oxide Synthase Type I
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Pertussis Toxin
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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Rats
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Receptors, Cannabinoid
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Receptors, Drug / agonists
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Receptors, Drug / antagonists & inhibitors
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Receptors, Drug / metabolism*
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Rimonabant
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Virulence Factors, Bordetella / pharmacology
Substances
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Benzoxazines
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Calcium Channel Blockers
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Morpholines
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Naphthalenes
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Piperidines
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Pyrazoles
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Receptors, Cannabinoid
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Receptors, Drug
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Virulence Factors, Bordetella
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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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Nitric Oxide Synthase
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Nitric Oxide Synthase Type I
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Nos1 protein, rat
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Pertussis Toxin
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Rimonabant