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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1999-2-25
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pubmed:abstractText |
Mutation screening identified variants of h5-HT1A (Gly-22-Ser, Ile-28-Val, Arg-219-Leu), h5-HT1B (Phe-124-Cys), h5-HT2A (Thr-25-Asn, His-452-Tyr), h5-HT2C (Cys-23-Ser) and h5-HT7 (Thr-92-Lys, Pro-279-Leu) receptors. Screening of h5-HT1D, h5-ht1e, h5-ht1f and h5-ht5 receptor genes failed to detect any significant mutations. No differences in radioligand binding properties were observed between the h5-HT1A Ile-28-Val variant receptor (VR) and the wildtype receptor (WTR). Binding profiles of the h5-HT1A Gly-22-Val variant and the WTR were also very similar, but the 8-OH-DPAT-induced down-regulation and desensitization of the VR was attenuated. The h5-HT1B Phe-124-Cys variant leads to considerable changes in [3H]5-carboxamidotryptamine binding: Bmax was decreased and the affinity of various h5-HT1B ligands was modified (usually increased; e.g., in the case of sumatriptan). The h5-HT2A His-452-Tyr variant causes an alteration of the amplitude and timing of intracellular calcium mobilization in platelets from 452-His/452-Tyr heterozygous compared to 452-His/452-His homozygous individuals. Most, but not all, of the VRs listed above were examined for association with, e.g., bipolar depression and schizophrenia, yet no relation was observed. The most consistent finding was an association between a silent mutation (102T/C) in the h5-HT2A receptor gene and schizophrenia; this association may be explained by linkage disequilibrium with a functional variant in the regulatory region of the gene. Studies of the therapeutic response to clozapine produced no homogeneous results with respect to the pharmacogenetic significance of the various mutations in the h5-HT2A and h5-HT2C receptor genes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/HTR1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT1
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0077-8923
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
861
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26-30
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9928235-Bipolar Disorder,
pubmed-meshheading:9928235-Genetic Variation,
pubmed-meshheading:9928235-Humans,
pubmed-meshheading:9928235-Point Mutation,
pubmed-meshheading:9928235-Receptor, Serotonin, 5-HT1B,
pubmed-meshheading:9928235-Receptors, Serotonin,
pubmed-meshheading:9928235-Receptors, Serotonin, 5-HT1,
pubmed-meshheading:9928235-Schizophrenia,
pubmed-meshheading:9928235-Signal Transduction
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pubmed:year |
1998
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pubmed:articleTitle |
Genetic variation in human 5-HT receptors: potential pathogenetic and pharmacological role.
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pubmed:affiliation |
Institute of Pharmacology and Toxicology, University of Bonn, Germany.
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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