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rdf:type |
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lifeskim:mentions |
umls-concept:C0026882,
umls-concept:C0033634,
umls-concept:C0205145,
umls-concept:C0379900,
umls-concept:C0596235,
umls-concept:C0599946,
umls-concept:C0728938,
umls-concept:C0871261,
umls-concept:C1519063,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692,
umls-concept:C2936511
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pubmed:issue |
7
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pubmed:dateCreated |
2003-5-2
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pubmed:abstractText |
The Thr(149)Ala mutation in a putative protein kinase C phosphorylation site of the 5-HT(1A) receptor's second intracellular loop has been shown to affect the closing of Ca(2+) channels and Ca(2+) mobilisation without interfering with the inhibitory cAMP pathway (Mol Pharmacol 52 (1997) 164). Here, the Ca(2+) responses for a series of 5-HT(1A) agonists were compared between the wild-type (wt) and mutant Thr(149)Ala 5-HT(1A) receptor as part of a fusion protein containing a G(alpha)(15) protein. Neither the mutation nor the fusion process modified the [(3)H]WAY 100635-based ligand binding profile of the fusion proteins as compared to the wt 5-HT(1A) receptor protein. Whereas at the wt 5-HT(1A) receptor, 5-HT induced a Ca(2+) response in CHO-K1 cells via endogenous G(i/o) proteins, the Ca(2+) response to 5-HT at the mutant Thr(149)Ala 5-HT(1A) receptor was fully dependent on either the co-expression or the fusion to a recombinant G(alpha)(15) protein. Buspirone, flesinoxan and 8-OH-DPAT produced a graded partial response (26 to 62%) at the wt 5-HT(1A):G(alpha)(15) fusion protein; F 13640, 5-CT and F 14679 behaved as higher-efficacy agonists with maximal Ca(2+) responses similar to 5-HT. The maximal Ca(2+) responses at the mutant Thr(149)Ala 5-HT(1A):G(alpha)(15) fusion protein were significantly attenuated for flesinoxan and 8-OH-DPAT (-45 and -36%, respectively); the response to the other 5-HT agonists was not significantly affected. A similar effect was observed upon treatment with phorbol 12-myristate 13-acetate at the Thr(149)Ala 5-HT(1A):G(alpha)(15) fusion protein. In conclusion, the amplitude of the Ca(2+) responses induced by partial, but not that to fuller 5-HT(1A) receptor agonists, is affected by the Thr(149)Ala mutation of the 5-HT(1A):G(alpha)(15) fusion protein.
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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/8-Hydroxy-2-(di-n-propylamino)tetral...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/G protein alpha 16,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Heterotrimeric GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT1,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/WAY 100635,
http://linkedlifedata.com/resource/pubmed/chemical/flesinoxan
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0028-3908
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
873-81
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12726819-8-Hydroxy-2-(di-n-propylamino)tetralin,
pubmed-meshheading:12726819-Animals,
pubmed-meshheading:12726819-CHO Cells,
pubmed-meshheading:12726819-Calcium,
pubmed-meshheading:12726819-Cricetinae,
pubmed-meshheading:12726819-GTP-Binding Protein alpha Subunits, Gq-G11,
pubmed-meshheading:12726819-Heterotrimeric GTP-Binding Proteins,
pubmed-meshheading:12726819-Humans,
pubmed-meshheading:12726819-Ligands,
pubmed-meshheading:12726819-Mutation,
pubmed-meshheading:12726819-Phosphorylation,
pubmed-meshheading:12726819-Piperazines,
pubmed-meshheading:12726819-Protein Kinase C,
pubmed-meshheading:12726819-Pyridines,
pubmed-meshheading:12726819-Radioligand Assay,
pubmed-meshheading:12726819-Receptors, Serotonin,
pubmed-meshheading:12726819-Receptors, Serotonin, 5-HT1,
pubmed-meshheading:12726819-Serotonin Antagonists,
pubmed-meshheading:12726819-Serotonin Receptor Agonists,
pubmed-meshheading:12726819-Tetradecanoylphorbol Acetate,
pubmed-meshheading:12726819-Transfection
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pubmed:year |
2003
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pubmed:articleTitle |
Mutation in a protein kinase C phosphorylation site of the 5-HT1A receptor preferentially attenuates Ca2+ responses to partial as opposed to higher-efficacy 5-HT1A agonists.
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pubmed:affiliation |
Department of Cellular and Molecular Biology, Centre de Recherche Pierre Fabre, 17, avenue Jean Moulin, 81106 Castres Cédex, France.
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pubmed:publicationType |
Journal Article
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