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PMID: 9204917 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 17 ·No. 14 ·1997-07-15 ·Pages 5327-33

Glass M, Felder CC

Abstract

Cannabinoids act at the CB1 receptor to inhibit adenylate cyclase activity via a pertussis toxin-sensitive G-protein. Within the striatum, CB1 receptors have been shown to be localized on the same neurons as Gi-coupled dopamine D2 receptors. In this study we have examined the interactions of CB1 and D2 receptors on adenylate cyclase. In striatal neurons in primary culture, both the CB1 receptor agonist [3-(1, 1-dimethylheptyl)-11-hydroxy-Delta8tetrahydrocannabinol] (HU210) and the D2 receptor agonist quinpirole inhibited forskolin-stimulated cAMP accumulation when applied separately. In contrast, HU210 and quinpirole in combination augmented cAMP accumulation. This augmentation was blocked by the CB1 receptor antagonist SR141716A or the D2 antagonist sulpride. Pertussis toxin treatment of striatal neurons prevented the inhibition of cAMP accumulation by D2 receptors but unmasked a cannabinoid receptor-mediated stimulatory effect on cAMP accumulation. The cannabinoid receptor-stimulated accumulation of cAMP was blocked in a concentration-dependent manner by SR141716A, suggesting that the response was regulated through the CB1 receptor. Similar augmentation of cAMP accumulation after pertussis toxin treatment was observed in Chinese hamster ovary (CHO) cells transfected with, and stably expressing, the CB1 receptor. This stimulation of cAMP was not Ca2+-sensitive and was unaffected by a range of protein kinase inhibitors. Treatment of the pertussis toxin-treated cells with cholera toxin before CB1 receptor activation amplified the stimulatory pathway, suggesting that this response was mediated through a Gs-type G-protein. Stimulation of cAMP accumulation was not observed after pertussis toxin treatment of CHO cells expressing the human CB2 receptor, suggesting that this novel signaling pathway is unique to the cannabinoid CB1 receptor.

MeSH Terms
Animals CHO Cells/drug effects Cells, Cultured/drug effects Colforsin/pharmacology Cricetinae Cyclic AMP/metabolism Dose-Response Relationship, Drug GTP-Binding Proteins/drug effects Rats Receptor, Cannabinoid, CB2 Receptors, Cannabinoid Receptors, Dopamine D2/drug effects Receptors, Drug/drug effects Visual Cortex/drug effects,metabolism
Chemicals
Cnr2 protein, rat Receptor, Cannabinoid, CB2 Receptors, Cannabinoid Receptors, Dopamine D2 Receptors, Drug Colforsin Cyclic AMP GTP-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Glass M
Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892-4090, USA.
Felder C C
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1997-07-15
Pages
5327-33
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6793808
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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