IS Pro15Ser Polymorphism Able to Affect the Signal Transduction of 5-HT5A Receptor?

Accession number;02A0472891
Title;IS Pro15Ser Polymorphism Able to Affect the Signal Transduction of 5-HT5A Receptor?
Author; NISHIYAMA TAKESHI (Nagoyashidai I Seishin'igaku) OKADA MITSUKO (Aioikai, Rinsho Yakuri Senta) FURUKAWA TOSHIAKI (Nagoyashidai I Seishin'igaku)
Journal Title;Annual Report of the Pharmacopsychiatry Research Foundation
Journal Code:Y0939A
ISSN:0286-7591
VOL.;NO.34;PAGE.176-178(2002)
Figure&Table&Reference;FIG.1, REF.4
Pub. Country;Japan
Language;Japanese
Abstract;Background: The 5-HT5A receptor is expressed predominantly within the brain region, especially by reactive astrocytes. Little has been known about physiological functions of the 5-HT5A receptor, the receptor appears to mediate the hallucinogenic effects of LSD. Recently, we have reported that the naturally occurring Pro 15-Ser15 substitution in the human 5-HT5A receptor is associated significantly with Japanese schizophrenia. Object: The influence of Pro15Ser polymorphism on the function of the 5-HT5A receptor was investigated in the C6 glioma cells expressing cloned human 5-HT5A receptors. Methods: We compared the binding profile of 125I-LSD for Pro15 5-HT5A receptor with that for Ser15 5-HT5A receptor. The affinities of 5-HT and 5-CT for the receptor were also compared between Pro15 and Ser15 5-HT5A receptors. Results and Discussion: The Bmax values of 125I-LSD binding for Ser15 were about 40% smaller than for Pro15. However, the Kd values of 125I-LSD binding did not differ between Pro15 and Ser15. The IC50 of 5-HT and 5-CT to 125I-LSD binding were almost identical between Pro15 and Ser15 5-HT5A receptors. Pro15Ser polymorphism might cause influence on the receptor expression rather than the ligand affinity for the receptor. (author abst.)