An inhibitory compound against the interaction between Galpha(s) and the third intracellular loop region of serotonin receptor subtype 6 (5-HT(6)) disrupts the signaling pathway of 5-HT(6)
Experimental & Molecular Medicine
;
: 335-342, 2007.
Article
in English
| WPRIM
| ID: wpr-201421
ABSTRACT
Serotonin receptor subtype 6 (5-HT(6)) is a neurotransmitter receptor, which is involved in various brain functions such as memory and mood. It mediates signaling via the interaction with a stimulatory G-protein. Especially, the third intracellular loop (iL3) of 5-HT(6) and the alpha subunit of stimulatory G protein (Galpha(s)) are responsible for the signaling process of 5-HT(6). Chemical compounds that could inhibit the interaction between the iL3 region of 5-HT(6) and Galpha(s) were screened from a chemical library consisted of 5,600 synthetic compounds. One of the identified compounds bound to Galpha(s) and effectively blocked the interaction between Galpha(s) and the iL3 region of 5-HT(6). The identified compound was further shown to reduce the serotonin-induced accumulation of cAMP in 293T cells transformed with 5-HT(6) cDNA. It also lowered the Ca2+ efflux induced by serotonin in cells expressing 5-HT(6) and chimeric Galpha(s5/q). These results indicate that the interaction between the iL3 of 5-HT(6) and Galpha(s) can be exploited for screening of regulatory compounds against the signaling pathway of 5-HT(6).
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Serotonin Antagonists
/
Signal Transduction
/
Serotonin
/
Cell Line
/
Cephalosporins
/
Calcium
/
Cricetulus
/
Receptors, Serotonin
/
Cyclic AMP
/
GTP-Binding Protein alpha Subunits, Gs
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2007
Type:
Article
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