Effects of Cys23Ser in 5-HT2C receptor gene on the receptor function and the association between Cys23Ser and mental disorders.
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Accession number;02A0472871
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| Title;Effects of Cys23Ser in 5-HT2C receptor gene on the receptor function and the association between Cys23Ser and mental disorders. |
| Author;
OZAKI NORIO
(Fujitahoken'eiseidai I Seishin'igaku)
IWATA NAKAO
(Fujitahoken'eiseidai I Seishin'igaku)
KITAJIMA TAKESHI
(Fujitahoken'eiseidai I Seishin'igaku)
YAMANOUCHI YOSHIO
(Fujitahoken'eiseidai I Seishin'igaku)
SUZUKI TATSUYO
(Fujitahoken'eiseidai I Seishin'igaku)
GOLDMAN D
(National Inst. On Alcohol Abuse And Alcoholism, Usa)
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Journal Title;Annual Report of the Pharmacopsychiatry Research Foundation
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Journal Code:Y0939A
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ISSN:0286-7591
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VOL.;NO.34;PAGE.39-44(2002)
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| Figure&Table&Reference;FIG.4, TBL.2, REF.12 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;A human 5-HT2C receptor gene polymorphism leads to substitution of cysteine for serine at position 23(Cys23Ser). To evaluate whether Cys23Ser affects receptor function, we studied the receptor functional profile of two alleles expressing in cellular environment. Furthermore, we analyzed association between this Cys23Ser, and schizophrenia and mood disorders in Japanese. In displacement analyses with [125I] DOI, the Ser23 expressed in COS-7 cells showed reduced high affinity binding to m-CPP. The in situ reconstitution assay indicated no difference between the Cys23 and Ser23 in affinity for G*q or G**. However, the basal inhibition of the Ser23 by the inverse agonist, mianserin, was significantly larger than for the Cys23, suggesting higher constitutive activity of the Ser23. No significant difference in the amplitude of the intracellular Ca2+ peak after administration of 5-HT between two alleles was observed. However, the Ser23 required higher 5-HT concentrations to elicit the same response. These in vitro expression results indicate that the Cys23Ser may reduce the 5-HT2C receptor function. No differences in allele frequencies were seen in the schizophrenia and mood disorders patients compared to the controls. However, it is necessary to increase the number of samples to elucidate the role of the Cys23Ser, because allele frequencies in Japanese are much less than Caucasian. (author abst.) |
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