Ginsenosides Rg1 and Rb1 enhance glutamate release through activation of protein kinase A in rat cerebrocortical nerve terminals (synaptosomes).
We examined the effect of ginsenoside Rg1 or Rb1, the active ingredients of ginseng, on the release of endogenous glutamate from glutamatergic nerve terminals purified from rat cerebral cortex. Result showed that the Ca(2+)-dependent release of glutamate evoked by 4-aminopyridine was facilitated by ginsenoside Rg1 or Rb1 in a concentration-dependent manner. Sequential experiments reveal that ginsenoside Rg1 or Rb1-mediated facilitation of glutamate release (i) results from an enhancement of vesicular exocytosis; (ii) is not due to an alternation of synaptosomal excitability; (iii) is associated with an increase in Ca(2+) influx through presynaptic N- and P/Q-type voltage-dependent Ca(2+) channels; (iv) appears to involve a protein kinase A pathway. These results conclude that ginsenoside Rg1 or Rb1 exerts their presynaptic facilitatory effect, likely through the activation of protein kinase A, which subsequently enhances Ca(2+) entry to cause an increase in evoked glutamate release from rat cortical synaptosomes. This finding might provide important information regarding the action of ginseng in the central nervous system.
Chang
Yi
Y
School of Medicine, Fu Jen Catholic University, 510, Chung-Cheng Rd., Hsin-Chuang, Taipei Hsien 24205, Taiwan.
Huang
Wei-Jan
WJ
Tien
Lu-Tai
LT
Wang
Su-Jane
SJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D002491:Central Nervous System Agents; D036145:Ginsenosides; D018698:Glutamic Acid; C442759:ginsenoside Rb1; D017868:Cyclic AMP-Dependent Protein Kinases; C035054:ginsenoside Rg1; D002118:Calcium