Effects of propofol on glutamate release from rat cerebral cortex nerve terminal

• Main Authors: LU CHENG-WEI, 陸正威
• Other Authors: WANG SU-JANE
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/88112284474448395478

碩士 === 輔仁大學 === 基礎醫學研究所碩士班 === 96 === Propofol is now the most common used intravenous anesthetics for general anesthesia and sedation due to its rapid onset and recovery. Besides the well-known adverse effects of cardiovascular and respiratory depression, recent studies indicate that propofol may cause excitatory phenomena such as myoclonus, and epilepsy. However, the mechanisms of theses excitatory effects of propofol have not been elucidated. Considering glutamate is the principle excitatory neurotransmitter in the central nervous system and excessive glutamatergic synaptic transmission can cause epilepsy, we examined the effect of propofol on the release of glutamate from rat cerebral cortex nerve terminals (synaptosomes). Results showed that low dose propofol facilitated 4-aminopyridine (4-AP) but not KCl- or ionomycin-evoked glutamate release from nerve terminal. The facilitation of 4-AP-evoked glutamate release by propofol also occurred in the calcium chelation and significantly attenuated by glutamate transporter inhibitors, DL-TBOA and L-trans-PDC. In addition, propofol increased 4-AP-evoked depolarization of the plasma membrane potential. Furthermore, protein kinase C (PKC) inhibition suppressed propofol-mediated facilitation of glutamate release. These results suggest that low dose propofol facilitates glutamate release from rat cerebrocortical glutamatergic terminals by increasing nerve terminal excitability, likely through the activation of PKC pathway. This finding may provide an explanation for subanesthetic propofol induced excitatory phenomena.