Facilitation of glutamate release from rat cerebral cortex nerve terminal by subanesthetic concentration propofol.
Propofol is now the most commonly used intravenous anesthetic-for general anesthesia and sedation because of 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, opisthotonus, and even seizure. However, the mechanisms of these excitatory effects of propofol have not been elucidated. Considering glutamate as the principle excitatory neurotransmitter in the central nervous system and excessive glutamatergic synaptic transmission can cause seizure, we examined the effect of propofol on the release of glutamate from rat cerebral cortex nerve terminals (synaptosomes). Results showed that subanesthetic concentration propofol facilitated 4-aminopyridine (4-AP), but not KCl- or ionomycin-evoked glutamate release from nerve terminals. The facilitation of 4-AP-evoked glutamate release by propofol also occurred in the calcium chelation and significantly attenuated by glutamate transporter inhibitors, DL-threo-beta-benzyloxyaspartic acid (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylic acid (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 subanesthetic concentration 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 propofol-induced excitatory phenomena.
Lu
Cheng-Wei
CW
Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao, Taipei County, Taiwan.
Lin
Tzu-Yu
TY
Chiang
Han-Sun
HS
Wang
Su-Jane
SJ
D015761:4-Aminopyridine / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes; D050496:Vesicular Glutamate Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D018686:Anesthetics, Intravenous; D026902:Potassium Channel Blockers; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid; D015761:4-Aminopyridine; D011493:Protein Kinase C; D015742:Propofol