The orthosteric GABAA receptor ligand Thio-4-PIOL displays distinctly different functional properties at synaptic and extrasynaptic receptors.

ABSTRACT:

Background and purpose

Explorations into the heterogeneous population of native GABA type A receptors (GABAA Rs) and the physiological functions governed by the multiple GABAA R subtypes have for decades been hampered by the lack of subtype-selective ligands.

Experimental approach

The functional properties of the orthosteric GABAA receptor ligand 5-(4-piperidyl)-3-isothiazolol (Thio-4-PIOL) have been investigated in vitro, ex vivo and in vivo.

Key results

Thio-4-PIOL displayed substantial partial agonist activity at the human extrasynaptic GABAA R subtypes expressed in Xenopus oocytes, eliciting maximal responses of up to ∼30% of that of GABA at α5 β3 γ2S , α4 β3 δ and α6 β3 δ and somewhat lower efficacies at the corresponding α5 β2 γ2S , α4 β2 δ and α6 β2 δ subtypes

SUBMITTER: Hoestgaard-Jensen K 

PROVIDER: S-EPMC3799604 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature