EFFECTS OF 5-(4-PIPERIDYL) ISOXAZOL-3-OL (4-PIOL), A GABA(A) RECEPTORPARTIAL AGONIST, ON RECOMBINANT HUMAN GABA(A) RECEPTORS

gamma-Aminobutyric acid A (GABA(A)) gated chloride ion channels were e xpressed from human recombinant cDNA using the baculovirus/Sf-9 insect cell expression system. The electrophysiological effects in whole-cel l currents of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) recept or partial agonist, were investigated on GABA(A) receptor complexes of alpha(1) beta(2) gamma(2S) subunits as well as a slightly modified co nstruct of alpha 1(valine 121) beta(2) gamma(2S) subunits. Here we rep ort that (1) 4-PIOL induces an inward whole-cell current in a concentr ation-dependent manner in both alpha 1(val 121) beta(2) gamma(2S) and alpha 1(ile 121) beta(2) gamma(2S) receptor subunit combinations. (2) The 4-PIOL induced whole-cell currents were more pronounced in alpha 1 (val 121) beta(2) gamma(2S) than in alpha 1(ile 121) beta(2) gamma(2S) receptor subunit combinations. (3) 4-PIOL inhibited GABA-induced resp onses on alpha 1(ile 121) beta(2) gamma(2S) and alpha 1(val 121) beta( 2) gamma(2S) receptor combinations with similar potency. (C) 1997 Else vier Science Ireland Ltd.