PHARMACOLOGICAL DISCRIMINATION OF GLUR5 AND GLUR6 KAINATE RECEPTOR SUBTYPES BY 1(2)H-TETRAZOLE-5-YL)ETHYL]DECAHYDROISOQUINOLINE-3 CARBOXYLIC-ACID

The pharmacological tools available for the discrimination of kainate receptor subtypes are limited. We examined the effects of zole-5-yl)et hyl]decahydroisoquinoline-3-carboxylic acid (LY293558) and -dihydroxy- 6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) on inward currents asso ciated with activation of non-N-methyl-D-aspartate (NMDA) receptors in acutely isolated rat cerebellar Purkinje neurons, rat dorsal root gan glion neurons, and human embryonic kidney 293 cells transfected with h uman glutamate receptors (GluR) 5 and 6. LY293558 and NBQX inhibited k ainate-induced currents in cerebellar Purkinje cells, DRG neurons, and human GluR5-transfected cells. In contrast, human embryonic kidney 29 3 cells expressing GluR6 receptors, although blocked by NBQX, were una ffected by LY293558 at concentrations of less than or equal to 100 mu M. The selective antagonism by LY293558 of GluR5 receptors should allo w the determination of the functional role of GluR5 and GluR6 in more complex systems.