Coupling between agonist and chloride ionophore sites of the GABA(A) receptor: agonist/antagonisr efficacy of 4-PIOL
: Rabe H, Picard R, Uusi-Oukari M, Hevers W, Lüddens H, Korpi ER
: 2000
European Journal of Pharmacology
: 409
: 3
: 233
: 242
DOI: https://doi.org/https://doi.org/10.1016/S0014-2999(00)00838-4
: https://www.sciencedirect.com/science/article/pii/S0014299900008384?via=ihub
Eight gamma-aminobutyric acid (GABA) mimetics were tested on their
ability to differentiate native GABAA receptor subtypes present in
various rat brain regions. In rat brain cryostat sections, little
regional variations by the agonistic actions of muscimol, thiomuscimol,
4,5,6,7-tetrahydroisoazolo(5,4-c)pyridin-3-ol, piperidine-4-sulphonic
acid, taurine and beta-alanine on [35S]t-butylbicyclophosphorothionate
([35S]TBPS) binding to GABAA receptor channels were found. They were
very similar to those found for GABA itself and indicated no direct
correlation with single subunit distributions for any of these
compounds. Only the low-efficacy GABA mimetic
5-(4-piperidyl)isoxazol-3-ol (4-PIOL) acted like a weak partial agonist
or antagonist depending on the brain area. As the cerebellar granule
cell layer was relatively insensitive to both modes of action, we tested
4-PIOL in recombinant alpha1beta2gamma2 (widespread major subtype) and
alpha6beta2gamma2 (cerebellar granule cell restricted) receptors where
it had different effects on GABA-modulated [35S]TBPS binding and on
electrophysiological responses. 4-PIOL may thus serve as a potential
lead for receptor subtype selective compounds.
