Facilitation of glutamate release from rat cerebrocortical glutamatergic nerve terminals (synaptosomes) by phosphatidylserine and phosphatidylcholine.
Phosphatidylserine (PS) and phosphatidylcholine (PC) have been shown to enhance cognitive function. Considering that brain glutamatergic system is thought to participate in cognitive processing, our objective was to determine the effect of PS and PC on glutamate release from the nerve terminal (synaptosome) freshly isolated from rat cerebral cortex. Data showed that both PS and PC potently facilitate 4-aminopyridine (4-AP)-evoked Ca(2+)-dependent and Ca(2+)-independent glutamate release. Facilitation of glutamate release by PS or PC was associated with an increase of 4-AP-evoked depolarization and downstream elevation of cytoplasmic free calcium concentration ([Ca(2+)](c)). In addition, glutamate release elicited by direct Ca(2+)-entry with Ca(2+)-ionophore (ionomycin) was also facilitated by PS or PC. Furthermore, PS- or PC-mediated facilitation of 4-AP-evoked glutamate release was superseded or suppressed by protein kinase C (PKC) activator and inhibitor, respectively. Together, these results suggest that PS or PC effects a facilitation of glutamate exocytosis by increasing nerve terminal excitability and Ca(2+) influx into cerebrocortical nerve terminals through a signaling cascade involving PKC.
Yang
Tsung-Tsair
TT
School of Medicine, Fu Jen Catholic University, Hsin-Chuang, Taipei Hsien, Taiwan.
Wang
Su-Jane
SJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D002525:Cerebellar Cortex / Q000166:cytology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors
D002232:Carbocyanines; D007476:Ionophores; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D026902:Potassium Channel Blockers; C088733:3,3'-dipentylthiacarbocyanine; D018698:Glutamic Acid; D015759:Ionomycin; D015761:4-Aminopyridine; D002118:Calcium