2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and 8-bromoadenosine-3--5--cyclic-monophosphorothioate

We have explored the mechanisms involved in the facilitation of glutamate release mediated by the activation of kainate receptors (KARs) in the cortex using isolated nerve terminals (synaptosomes). Kainate (KA) produced an increase on glutamate release at 100 μM. The effect of KA was antagonized by NBQX (with AMPA receptors blocked by GYKI53655). This facilitation was suppressed by the inhibition of PKA activation by Rp-Br-cAMP and H-89. Moreover, the facilitation of glutamate release mediated by KAR requires the mobilization of intrasynaptosomal Ca(2+) stores and the formation of a Ca(2+)-calmodulin complex. We conclude that KARs present on presynaptic terminals in the neocortex mediate the facilitation of glutamate release through a mechanism involving an increase in cytosolic Ca(2+) to activate a Ca(2+)-calmodulin-AC/cAMP/PKA signaling cascade.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Benzodiazepines; Calcium; Calmodulin; Cerebral Cortex; Cyclic AMP-Dependent Protein Kinases; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Glutamic Acid; Isoquinolines; Kainic Acid; Male; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, Kainic Acid; Receptors, Presynaptic; Sulfonamides; Synaptic Transmission; Synaptosomes; Thionucleotides