Ginsenoside Rg1 and Rb1 enhance glutamate exocytosis from rat cortical nerve terminals by affecting vesicle mobilization through the activation of protein kinase C.
Our previous study showed that ginsenoside Rg1 and Rb1, the active ingredients of ginseng, facilitated depolarization-evoked glutamate release from isolated rat cortical nerve terminals by increasing voltage-dependent Ca(2+) entry. However, it remains to be clarified whether ginsenoside Rg1 and Rb1 possess an action at the exocytotic machinery itself, downstream of a Ca(2+) influx. We now show that ionomycin-induced glutamate release and KCl-evoked FM1-43 dye release were facilitated by ginsenoside Rg1 and Rb1 in rat cortical nerve terminals (synaptosomes), suggesting that some steps after Ca(2+) entry are regulated by ginsenoside Rg1 or Rb1. The activation of protein kinase C is essential for ginsenoside Rg1 or Rb1 action, since protein kinase C inhibitors GF109203X and Ro318220 abolished the facilitatory effect of ginsenoside Rg1 or Rb1 on ionomycin-evoked glutamate release. Furthermore, ginsenoside Rg1 or Rb1 increased ionomycin-evoked protein kinase C or its presynaptic target myristoylated alanine-rich C kinase substrate (MARCKS) phosphorylation. Additionally, ginsenoside Rg1 or Rb1-mediated facilitation of ionomycin-evoked glutamate release was occluded by cytochalasin D, a membrane-permeant inhibitor of actin polymerization. Together, these results suggest that ginsenoside Rg1 or Rb1-mediated facilitation of glutamate release involves the modulation of some exocytotic steps, possibly through the activation of protein kinase C and disassembly of cytoskeleton, resulting in an increase in synaptic vesicle availability.
Chang
Yi
Y
School of Medicine, Fu Jen Catholic University, 510, Chung-Cheng Rd., Hsin-Chuang, Taipei Hsien, 24205 Taiwan.
Wang
Su-Jane
SJ
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects*; D036145:Ginsenosides / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism
D036145:Ginsenosides; D047908:Intracellular Signaling Peptides and Proteins; C000619712:Marcks protein, rat; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D015638:Cytochalasin D; D018698:Glutamic Acid; D015759:Ionomycin; C442759:ginsenoside Rb1; D011493:Protein Kinase C; C035054:ginsenoside Rg1