Cyclothiazide potentiates agonist responses at human AMPA/kainate receptors expressed in oocytes.
Cloned human AMPA/kainate subunits were functionally expressed in Xenopus oocytes. Cyclothiazide potentiated kainate-evoked currents by 682 +/- 122% (mean +/- S.E.M., n = 5), 1396 +/- 55% (n = 4), and 690 +/- 40% (n = 14) in oocytes expressing GluR1, GluR2, and GluR1 + GluR2 receptors, respectively. AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate)-induced currents were also potentiated by cyclothiazide. GYKI 52466 (1-(4-amino-phenyl)-4-methyl-7,8-methylendioxyl-5H-2,3-benzod++ + iazepine hydrochloride) attenuated cyclothiazide potentiation in all cases. Thus, modulatory sites for cyclothiazide and GYKI 52466 exist on individual human AMPA/kainate receptor subunits. Additionally, kainate appears to act as a desensitizing partial agonist at human GluR1 and GluR2 receptor subunits.
Sharp
R L
RL
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
May
P C
PC
Mayne
N G
NG
Snyder
Y M
YM
Burnett
J P
JP
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology; D001581:Benzothiadiazines / Q000494:pharmacology*; D003001:Cloning, Molecular; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D009865:Oocytes; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects* / Q000378:metabolism; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D001581:Benzothiadiazines; D007608:Kainic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C061950:GYKI 52466; C004639:cyclothiazide