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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1999-5-6
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pubmed:abstractText |
The human cannabinoid receptor CB1 functionally couples primarily to Gi-, but also to Gs-mediated pathways to modulate intracellular cyclic AMP (cAMP) levels. To probe the features of the receptor that may be involved in promoting interactions with one G protein type over another, we generated the L341A/A342L mutant CB1 receptor. The double mutation involved the swap in position of two adjacent residues in the carboxyl-terminal segment of the third intracellular loop of CB1. This resulted in partial constitutive activation of the receptor and an agonist-independent enhancement in cAMP levels. Characterization following treatment with either pertussis or cholera toxin indicated that the constitutive activity is selective for a Gs- and not a Gi-mediated pathway. Treatment with the CB1-specific inverse agonist SR141716A inhibited the basal accumulation of cAMP in the presence of pertussis toxin, establishing that the effect is CB1 mediated. The binding of the agonist CP-55,940 to the L341A/A342L receptor was not markedly different from that for the wild-type receptor despite the constitutive Gs activity. This may reflect a preference of this ligand for an activated receptor state associated with the Gi coupling form and underscores the potential for developing therapeutics that selectively activate one pathway over another.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(2-hydroxy-4-(1,1-dimethylheptyl)p...,
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclohexanols,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cannabinoid,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella,
http://linkedlifedata.com/resource/pubmed/chemical/rimonabant
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
72
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2032-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10217281-Animals,
pubmed-meshheading:10217281-CHO Cells,
pubmed-meshheading:10217281-Cholera Toxin,
pubmed-meshheading:10217281-Cricetinae,
pubmed-meshheading:10217281-Cyclic AMP,
pubmed-meshheading:10217281-Cyclohexanols,
pubmed-meshheading:10217281-GTP-Binding Proteins,
pubmed-meshheading:10217281-Humans,
pubmed-meshheading:10217281-Mutation,
pubmed-meshheading:10217281-Peptide Fragments,
pubmed-meshheading:10217281-Pertussis Toxin,
pubmed-meshheading:10217281-Piperidines,
pubmed-meshheading:10217281-Pyrazoles,
pubmed-meshheading:10217281-Receptors, Cannabinoid,
pubmed-meshheading:10217281-Receptors, Drug,
pubmed-meshheading:10217281-Virulence Factors, Bordetella
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pubmed:year |
1999
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pubmed:articleTitle |
Involvement of the carboxyl terminus of the third intracellular loop of the cannabinoid CB1 receptor in constitutive activation of Gs.
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pubmed:affiliation |
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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