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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2006-10-24
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pubmed:abstractText |
Agonists at G-protein-coupled receptors in neurons of the dorsal raphe nucleus (DRN) of knock-out mice devoid of the serotonin transporter (5-HTT(-/-)) exhibit lower efficacy to inhibit cellular discharge than in wild-type counterparts. Using patch-clamp whole-cell recordings, we found that a G-protein-gated inwardly rectifying potassium (GIRK) current is involved in the inhibition of spike discharge induced by 5-HT1A agonists (5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT); 50 nM-30 microM) in both wild-type and 5-HTT(-/-) female and male mice. These effects were mimicked by 5'-guanylyl-imido-diphosphate (Gpp(NH)p; 400 microM) dialysis into cells with differences between genders. The 5-HTT(-/-) knock-out mutation reduced the current density induced by Gpp(NH)p in females but not in males. These data suggest that the decreased response of 5-HT1A receptors to agonists in 5-HTT(-/-) mutants reflects notably alteration in the coupling between G-proteins and GIRK channels in females but not in males. Accordingly, gender differences in central 5-HT neurotransmission appear to depend-at least in part-on sex-related variations in corresponding receptor-G protein signaling mechanisms.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-3034
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2006 Wiley Periodicals, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
66
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1475-88
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pubmed:meshHeading |
pubmed-meshheading:17013926-8-Hydroxy-2-(di-n-propylamino)tetralin,
pubmed-meshheading:17013926-Animals,
pubmed-meshheading:17013926-Dose-Response Relationship, Drug,
pubmed-meshheading:17013926-Dose-Response Relationship, Radiation,
pubmed-meshheading:17013926-Drug Interactions,
pubmed-meshheading:17013926-Electric Stimulation,
pubmed-meshheading:17013926-Female,
pubmed-meshheading:17013926-G Protein-Coupled Inwardly-Rectifying Potassium Channels,
pubmed-meshheading:17013926-Guanylyl Imidodiphosphate,
pubmed-meshheading:17013926-Male,
pubmed-meshheading:17013926-Mice,
pubmed-meshheading:17013926-Mice, Inbred C57BL,
pubmed-meshheading:17013926-Mice, Knockout,
pubmed-meshheading:17013926-Neurons,
pubmed-meshheading:17013926-Piperazines,
pubmed-meshheading:17013926-Pyridines,
pubmed-meshheading:17013926-Raphe Nuclei,
pubmed-meshheading:17013926-Serotonin,
pubmed-meshheading:17013926-Serotonin Agents,
pubmed-meshheading:17013926-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:17013926-Sex Characteristics,
pubmed-meshheading:17013926-Time Factors
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pubmed:year |
2006
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pubmed:articleTitle |
Gender-dependent regulation of G-protein-gated inwardly rectifying potassium current in dorsal raphe neurons in knock-out mice devoid of the 5-hydroxytryptamine transporter.
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pubmed:affiliation |
UMR 677, INSERM/UPMC, NeuroPsychoPharmacologie, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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