EFFECT OF SPINAL KAINIC ACID RECEPTOR ACTIVATION ON SPINAL AMINO-ACIDAND PROSTAGLANDIN E(2) RELEASE IN RAT

Current work has shown that spinal excitatory amino acid receptor acti vation can evoke physiological phenomena that may be mediated by the s ubsequent depolarization of glutamate-containing neurons and the activ ation of cyclo-oxygenase systems. To investigate this phenomenon, rats were implanted with lumbar intrathecal loop dialysis catheters for pe rfusion and an additional lumbar intrathecal PE-10 catheter for drug d elivery. Two days after implantation, kainic acid (1 mu g) was injecte d intrathecally under light (0.5%) halothane anaesthesia and the spina l release of several amino acids and prostaglandin E(2) was examined. Resting concentrations (mean expressed as pmol/25 mu l) of glutamate ( 89), aspartate (9), serine (387), glycine (597), taurine (185), aspara gine (113) and prostaglandin E(2) (0.43) were observed. Intrathecal ka inic acid produced significant signs of arousal in the rat and evoked a significant increase (mean +/- S.E.M. of % baseline concentration) i n aspartate (445 +/- 127%) and glutamate (221 +/- 35%). Prostaglandin E(2) concentration was increased in the second post-injection sample ( 180 +/- 36%). Intrathecal pretreatment with 6-cyano-7-nitroquinoxaline -2,3-dione (3 mu g or 10 mu g), a non-N-methyl-D-aspartate receptor an tagonist, blocked amino acid but not prostaglandin E(2) release after kainic acid injection. Pretreatment with MK-801 (10 mu g; non-competit ive NMDA receptor antagonist) had no significant effect on evoked rele ase of amino acids or prostaglandin E(2). Indomethacin (10 mu g, a cyc lo-oxygenase inhibitor) pretreatment significantly decreased baseline prostaglandin E(2) release in control animals (61 +/- 6%) and suppress ed kainic acid-evoked aspartate, taurine and prostaglandin E(2) releas e, but had no effect on the concentration of glutamate after kainic ac id injection. These data suggest that activation of spinal kainic acid receptors provides a powerful stimulus for secondary excitatory amino acid release and, consistent with the concurrent appearance of prosta glandin E(2), that this release is potentiated by the release of a cyc lo-oxygenase product. Copyright (C) 1996 IBRO.