Effects of cyclo-oxygenase inhibition upon glutamate release from rat cerebellum.
Arachidonic acid has been proposed as a diffusible second messenger in the CNS with a pathophysiological role in epilepsy and stroke and a physiological role in long-term potentiation. These actions are possibly due to the ability of arachidonic acid to enhance extraneuronal glutamate concentration. In this present study we have investigated the effect of flurbiprofen, a cyclo-oxygenase inhibitor, on both potassium- and veratridine-stimulated release of glutamate from rat cerebellar slices. Flurbiprofen (100-500 microM) had no effect on basal release but significantly increased stimulated release. The NMDA receptor antagonist CPP abolished the flurbiprofen-induced potentiation to both modes of stimulation, whilst the metabotropic glutamate receptor antagonist, L-AP3, blocked potassium-stimulated enhancement but had a variable effect on veratridine-stimulated release.
Dickie
B G
BG
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Annels
S J
SJ
Davies
J A
JA
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects; D014701:Veratridine / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D005971:Glutamates; D018377:Neurotransmitter Agents; D015222:Sodium Channels; D018698:Glutamic Acid; D005480:Flurbiprofen; D014701:Veratridine; D011188:Potassium