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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-16
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pubmed:abstractText |
The 5-hydroxytryptamine-3 (5-HT3) receptor mediates the fast excitatory neurotransmission of serotonin and is known to mediate the nausea/emesis induced by radio/chemotherapy and anesthetics. A polymorphism encoding the variation Y129S in the 5-HT3B subunit exists in high frequency in the general population and has been shown to be inversely correlated to the incidence of major depression in women. We show that 5-HT3AB(Y129S) receptors exhibit a substantially increased maximal response to serotonin compared with WT receptors in two fluorescence-based cellular assays. In electrophysiological recordings, the deactivation and desensitization kinetics of the 5-HT3AB(Y129S) receptor are 20- and 10-fold slower, respectively, than those of the WT receptor. Single-channel measurements reveal a 7-fold-increased mean open time of 5-HT3AB(Y129S) receptors compared with WT receptors. The augmented signaling displayed by 5-HT3AB(Y129S) receptors may confer protection against the development of depression. The variant also may influence the development and/or treatment of nausea and other disorders involving 5-HT3 receptors. Thus, the impact of the high-frequency variant 5-HT3B(Y129S) on 5-HT3AB receptor signaling calls for a search for additional phenotypes, and the variant may thus aid in establishing the role of the 5-HT3AB receptor in pathophysiology.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-10781283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-11357122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-11505217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-11516569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-11888546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-11989819,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-12775740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-12801637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-1346089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-15316796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-15383648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-15515404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-15541891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-15605121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16116092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16205777,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16475958,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16487942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16516303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16534507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16874005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-16900104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-17327132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-17373882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-17392525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-17496724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-17650111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-2419552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-7565620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-8434003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-8488569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-9693387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18184810-9950429
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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/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/HTR3B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ions,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT3,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
722-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18184810-Cell Line,
pubmed-meshheading:18184810-Cell Membrane,
pubmed-meshheading:18184810-DNA, Complementary,
pubmed-meshheading:18184810-Depression,
pubmed-meshheading:18184810-Electrophysiology,
pubmed-meshheading:18184810-Female,
pubmed-meshheading:18184810-Genetic Variation,
pubmed-meshheading:18184810-Humans,
pubmed-meshheading:18184810-Ions,
pubmed-meshheading:18184810-Kinetics,
pubmed-meshheading:18184810-Polymorphism, Genetic,
pubmed-meshheading:18184810-Receptors, Serotonin,
pubmed-meshheading:18184810-Receptors, Serotonin, 5-HT3,
pubmed-meshheading:18184810-Serotonin,
pubmed-meshheading:18184810-Signal Transduction,
pubmed-meshheading:18184810-Transfection
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pubmed:year |
2008
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pubmed:articleTitle |
High-frequency HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor.
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pubmed:affiliation |
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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