Kainate produces concentration-dependent elevation of glutamate release but not cGMP levels in cultured neuron.
1. Treatment of cultured cerebellar granule cells for 3 min with N-methyl-D-aspartate (NMDA) resulted in a concentration-dependent elevation of cyclic GMP. However, neither kainate (KA) nor NMDA produced a concentration-dependent elevation of this nucleotide after exposing cells to the agonist for 60 min. 2. Unlike the case for cGMP, both KA and NMDA produced concentration-dependent elevations of glutamate for 60 min incubation. 3. The NMDA-induced elevations of cGMP and glutamate were blocked by selective NMDA receptor antagonists. 4. The selective KA/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, 6,7-nitroquinoxaline-2,3-dione (DNQX), blocked the KA-induced elevations of cGMP with 3-min exposures, but it augmented the response with 60-min exposures. However, the KA-induced release of glutamate was prevented by DNQX. 5. The KA/AMPA receptor antagonist, GYKI 52466, blocked all KA-induced responses regardless of the incubation times.
Oh
S
S
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4045, USA.
McCaslin
P P
PP
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology; D006152:Cyclic GMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D010879:Piperazines; D011810:Quinoxalines; C061950:GYKI 52466; D001569:Benzodiazepines; C056723:FG 9041; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D006152:Cyclic GMP; D007608:Kainic Acid