Osthole or imperatorin-mediated facilitation of glutamate release is associated with a synaptic vesicle mobilization in rat hippocampal glutamatergic nerve endings

Synapse. 2010 May;64(5):390-6. doi: 10.1002/syn.20738.


Osthole and imperatorin, two active compounds of Cnidium monnieri (L.) Cusson, have previously been shown to facilitate depolarization-evoked glutamate release from rat hippocampal nerve terminals by increasing voltage-dependent Ca(2+) entry. In this study, we further investigated whether osthole and imperatorin possess an action at the exocytotic machinery itself, downstream of a Ca(2+) influx. Our data showed that ionomycin-induced glutamate release and KCl-evoked FM1-43 release were facilitated by osthole and imperatorin, suggesting that some steps after Ca(2+) entry are regulated by these two compounds. Consistent with this, osthole or imperatorin-mediated facilitation of ionomycin-induced glutamate release was occluded by cytochalasin D that inhibits actin polymerization, implying that the disassembly of cytoskeleton is involved. In addition, the facilitatory action of osthole or imperatorin on ionomycin-induced glutamate release was attenuated by the Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor KN62. Furthermore, Western blotting analysis further showed that osthole or imperatorin significantly increased ionomycin-induced phosphorylation of CaMKII and synapsin I, the main presynaptic target of CaMKII. These results suggest, therefore, that osthole or imperatorin-mediated facilitation of glutamate release involves modulation of downstream events controlling synaptic vesicle recruitment and exocytosis, possibly through an increase of CaMKII activation and synapsin I phosphorylation, thereby increasing synaptic vesicle availability for exocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Actins / metabolism
  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Central Nervous System Agents / pharmacology*
  • Coumarins / pharmacology*
  • Cytochalasin D / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Furocoumarins / pharmacology*
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Ionomycin / pharmacology
  • Male
  • Neurons / drug effects
  • Neurons / physiology
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Synapsins / metabolism
  • Synaptic Vesicles / drug effects*
  • Synaptic Vesicles / physiology


  • Actins
  • Central Nervous System Agents
  • Coumarins
  • Enzyme Inhibitors
  • Furocoumarins
  • Synapsins
  • Cytochalasin D
  • Glutamic Acid
  • Ionomycin
  • KN 62
  • Potassium Chloride
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • imperatorin
  • Calcium
  • osthol