Novel mechanism of modulation at a ligand-gated ion channel; action of 5-Cl-indole at the 5-HT(3)A receptor
Andrew D Powell, Gillian Grafton, Alexander Roberts, Shannon Larkin, Nathanael O'Neill, Josephine Palandri, Reka Otvos, Alison J Cooper, Chris Ulens, Nicholas M Barnes
British Journal of Pharmacology | WILEY-BLACKWELL | Published : 2016
BACKGROUND AND PURPOSE: The 5-HT3 receptor is a prototypical member of the Cys-loop ligand-gated ion channel (LGIC) superfamily and an established therapeutic target. In addition to activation via the orthosteric site, receptor function can be modulated by allosteric ligands. We have investigated the pharmacological action of Cl-indole upon the 5-HT3 A receptor and identified that this positive allosteric modulator possesses a novel mechanism of action for LGICs. EXPERIMENTAL APPROACH: The impact of Cl-indole upon the 5-HT3 receptor was assessed using single cell electrophysiological recordings and [3 H]-granisetron binding in HEK293 cells stably expressing the 5-HT3 receptor. KEY RESULTS: C..View full abstract
SL was supported by a Physiological Society vacation studentship award to ADP. Unrestricted grant funding was also received from Celentyx Ltd to NMB.