Effects of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial agonist, on recombinant human GABA(A) receptors.
gamma-Aminobutyric acidA (GABA(A)) gated chloride ion channels were expressed from human recombinant cDNA using the baculovirus/Sf-9 insect cell expression system. The electrophysiological effects in whole-cell currents of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial agonist, were investigated on GABA(A) receptor complexes of alpha1beta2gamma2S subunits as well as a slightly modified construct of alpha1(valine 121)beta2gamma2S subunits. Here we report that (1)4-PIOL induces an inward whole-cell current in a concentration-dependent manner in both alpha1(val 121)beta2gamma2S and alpha1(ile 121)beta2gamma2S receptor subunit combinations. (2) The 4-PIOL induced whole-cell currents were more pronounced in alpha1(val 121)beta2gamma2S than in alpha1(ile 121)beta2gamma2S receptor subunit combinations. (3) 4-PIOL inhibited GABA-induced responses on alpha1(ile 121)beta2gamma2S and alpha1(val 121)beta2gamma2S receptor combinations with similar potency.
Westh-Hansen
S E
SE
Department of Biochemistry, Research Institute of Biological Psychiatry, St. Hans Hospital, Roskilde, Denmark.
Noguchi
K
K
Witt
M R
MR
Murai
Y
Y
Nielsen
M
M
Akaike
N
N
D000818:Animals; D002460:Cell Line; D018755:GABA Agonists / Q000494:pharmacology*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018411:Spodoptera; D014162:Transfection; D014633:Valine; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018755:GABA Agonists; D007555:Isoxazoles; D046911:Macromolecular Substances; D010880:Piperidines; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; C073009:5-(4-piperidyl)isoxazol-3-ol; D005680:gamma-Aminobutyric Acid; D014633:Valine