Auto-inhibition at a ligand-gated ion channel: a cross-talk between orthosteric and allosteric sites.

ABSTRACT:

Background and purpose

A ligand is believed to produce either positive or negative responses, or to block both of them. However, an indole compound was found to promote both positive and negative effects at the 5-HT3 AB receptor, which displays a low level of spontaneous activity. The present study attempted to delineate the mechanisms underlying this phenomenon.

Experimental approach

The spontaneously active V291S 5-HT3 A receptor was used to explore the properties of 5-hydroxyindole (5-HoI) and 5-methoxyindole (5-MoI), structural analogues of 5-HT, either alone or in combination with orthosteric probes.

Key results

Two types of efficacy switching were initiated by altering ligand structure and concentration. At lower concentrations, a subtle structural change at pos

SUBMITTER: Hu XQ 

PROVIDER: S-EPMC4280970 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature