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KMID : 0620920070390030335
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Experimental & Molecular Medicine
2007 Volume.39 No. 3 p.335 ~ p.342
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An inhibitory compound against the interaction between Gas and the third intracellular loop region of serotonin receptor subtype 6 (5-HT6) disrupts the signaling pathway of 5-HT6
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Choi Yun-Hee
Kang Ha-Tan
Lee Won-Kyu
Kim Tae-Hyun
Rhim Hye-Won
Yu Yeon-Gyu
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Abstract
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Serotonin receptor subtype 6 (5-HT6) 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-HT6 and the a subunit of stimulatory G protein (Gas) are responsible for the signaling process of 5-HT6. Chemical compounds that could inhibit the interaction between the iL3 region of 5-HT6 and Gas were screened from a chemical library consisted of 5,600 synthetic compounds. One of the identified compounds bound to Gas and effectively blocked the interaction between Gas and the iL3 region of 5-HT6. The identified compound was further shown to reduce the serotonin-induced accumulation of cAMP in 293T cells transformed with 5-HT6 cDNA. It also lowered the Ca2+ efflux induced by serotonin in cells expressing 5-HT6 and chimeric Gas5/q. These results indicate that the interaction between the iL3 of 5-HT6 and Gas can be exploited for screening of regulatory compounds against the signaling pathway of 5-HT6.
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KEYWORD
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GTP-binding protein subunits, Gs, serotonin, serotonin 6 receptor
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