Cycloheterophyllin inhibits glutamate release from nerve terminals of the rat hippocampus

The effect of cycloheterophyllin, a prenylflavone isolated from Artocarpus heteophyllus, on glutamate release was studied in the rat hippocampus using synaptosome and slice preparations. In rat hippocampal synaptosomes, cycloheterophyllin inhibited 4-aminopyridine (4-AP)-evoked glutamate release and elevation of intrasynaptosomal calcium levels. The inhibitory effect of cycloheterophyllin on 4-AP-evoked glutamate release was prevented in the presence of the vesicular transporter inhibitor, the N and P/Q-type calcium channel blocker, and the protein kinase C (PKC) inhibitor, but was insensitive to the intracellular Ca2+-release inhibitors, protein kinase A (PKA) inhibitor and mitogen-activated/extracellular signal-regulated kinase (MEK) inhibitor. Western blotting data in synaptosomes also showed that cycloheterophyllin significantly decreased the phosphorylation of PKC. In addition, cycloheterophyllin decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) without influencing the ...