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).
- Author:
Yun Hee CHOI
1
;
Hatan KANG
;
Won Kyu LEE
;
Taehyun KIM
;
Hyewhon RHIM
;
Yeon Gyu YU
Author Information
1. Life Sciences Division, Korea Institute of Science and Technology, Seoul 130-650, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
GTP-binding protein alpha subunits, Gs;
serotonin;
serotonin 6 receptor
- MeSH:
Animals;
Calcium/metabolism;
Cell Line;
Cephalosporins/*pharmacology;
Cricetinae;
Cricetulus;
Cyclic AMP/biosynthesis;
GTP-Binding Protein alpha Subunits, Gs/antagonists & inhibitors/*metabolism;
Humans;
Receptors, Serotonin/*drug effects/metabolism/*physiology;
Serotonin/pharmacology;
Serotonin Antagonists/pharmacology;
Signal Transduction
- From:Experimental & Molecular Medicine
2007;39(3):335-342
- CountryRepublic of Korea
- Language:English
-
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).
