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

Mol Pharmacol. 1996 Apr;49(4):581-5.

Abstract

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.

MeSH terms

  • Animals
  • Cell Line
  • Ganglia, Spinal / drug effects
  • Humans
  • Isoquinolines / pharmacology*
  • Purkinje Cells / drug effects
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / antagonists & inhibitors*
  • Receptors, Kainic Acid / antagonists & inhibitors*
  • Receptors, Kainic Acid / physiology
  • Tetrazoles / pharmacology*

Substances

  • Isoquinolines
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Tetrazoles
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • tezampanel