Pharmacological discrimination of GluR5 and GluR6 kainate receptor subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahyd roisdoquinoline-3 carboxylic-acid.
The pharmacological tools available for the discrimination of kainate receptor subtypes are limited. We examined the effects of (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydr  oisoquinoline-3-carboxylic acid (LY293558) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) on inward currents associated with activation of non-N-methyl-D-asparate (NMDA) receptors in acutely isolated rat cerebellar Purkinje neurons, rat dorsal root ganglion neurons, and human embryonic kidney 293 cells transfected with human glutamate receptors (GluR) 5 and 6. LY293558 and NBQX inhibited kainate-induced currents in cerebellar Purkinje cells, DRG neurons, and human GluR5-transfected cells. In contrast, human embryonic kidney 293 cells expressing GluR6 receptors, although blocked by NBQX, were unaffected by LY293558 at concentrations of < / = 100 microM. The selective antagonism by LY293558 of GluR5 receptors should allow the determination of the functional role of GluR5 and GluR6 in more complex systems.
Bleakman
R
R
Eli Lilly and Company, Lilly Research Centre, Windlesham, Surrey, UK.
Schoepp
D D
DD
Ballyk
B
B
Bufton
H
H
Sharpe
E F
EF
Thomas
K
K
Ornstein
P L
PL
Kamboj
R K
RK
D000818:Animals; D002460:Cell Line; D005727:Ganglia, Spinal / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
D007546:Isoquinolines; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D013777:Tetrazoles; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C082309:tezampanel