Myricetin inhibits the release of glutamate in rat cerebrocortical nerve terminals.

Abstract

The excessive release of glutamate is a critical element in the neuropathology of acute and chronic brain disorders. The purpose of the present study was to investigate the effect and possible mechanism of myricetin, a naturally occurring flavonoid with a neuroprotective profile, on endogenous glutamate release in the nerve terminals (synaptosomes) of the rat cerebral cortex. The release of glutamate was evoked by the K(+) channel blocker 4-aminopyridine (4-AP) and measured by one-line enzyme-coupled fluorometric assay. We also used a membrane potential-sensitive dye to assay the synaptosomal plasma membrane potential, and a Ca(2+) indicator Fura-2 to monitor cytosolic Ca(2+) concentrations ([Ca(2+)]C). Results show that myricetin inhibited 4-AP-evoked glutamate release, and this effect was prevented by chelating extracellular Ca(2+) ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate had no effect on myricetin action. Myricetin did not alter the synaptosomal membrane potential, but decreased 4-AP-induced increases in the cytosolic free Ca(2+) concentration. Furthermore, the myricetin effect on 4-AP-evoked glutamate release was prevented by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release. These results suggest that myricetin inhibits glutamate release from cerebrocortical synaptosomes by attenuating voltage-dependent Ca(2+) entry. This implies that the inhibition of glutamate release is an important pharmacological activity of myricetin that may play a critical role in the apparent clinical efficacy of this compound.

• Authors: Yi Chang, Chia-Ying Chang, Su-Jane Wang, Shu-Kuei Huang
• Journal: Journal of medicinal food (J Med Food) Vol. 18 Issue 5 Pg. 516-23 (May 2015) ISSN: 1557-7600 [Electronic] United States
• PMID: 25340625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels, N-Type
• Flavonoids
• voltage-dependent calcium channel (P-Q type)
• Glutamic Acid
• myricetin
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Channels, N-Type (metabolism)
• Cells, Cultured
• Cerebral Cortex (cytology, drug effects, metabolism)
• Flavonoids (pharmacology)
• Glutamic Acid (metabolism)
• Male
• Nerve Endings (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Synaptosomes (drug effects, metabolism)