Effects of AMPA receptor modulators on the production of arachidonic acid from striatal neurons

The abilities of different compounds acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors to modulate the overflow of [3H]arachidonic acid from rat striatal neurons were examined. The combination of AMPA (0.1 mM) and carbachol (1mM) stimulated [3H]arachidonic acid production, this effect could be dose-dependently enhanced by the newly discovered allosteric modulator of AMPA receptors: cyclothiazide. Competitive (6-cyano-7-nitroquinoxaline-2,3-dione [CNQX] and 6-(1-imidazolyl)-7-nitroquinazoline-2,3-dione [YM 900]) and non-competitive antagonists, like 1-(amino)-phenyl)-4-methyl -7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), antagonized the responses induced by either AMPA + carbachol or AMPA + carbachol + cyclothiazide. In order to appreciate the respective part of AMPA-versus kainate-preferring receptors experiments were performed with kainic acid (0.1 mM) and the more specific kainate agonist domoic acid (0.1 mM). Kainic acid behaves like AMPA, but the response induced by the combination domoic acid + carbachol could not be potentiated by cyclothiazide. On the contrary, concanavalin A potentiated the responses evoked by kainic acid or domoic acid (in combination with carbachol) but did not enhance the AMPA-evoked response. It could be concluded that both AMPA- and kainate-preferring receptors are present in cultured rat striatal neurons and that these two types of receptors were involved together with muscarinic receptors in the overflow of [3H]arachidonic acid.