PMID- 34475273
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211101
IS  - 1976-9148 (Print)
IS  - 2005-4483 (Electronic)
IS  - 1976-9148 (Linking)
VI  - 29
IP  - 6
DP  - 2021 Nov 1
TI  - Eupafolin Suppresses P/Q-Type Ca(2+) Channels to Inhibit Ca(2+)/ 
      Calmodulin-Dependent Protein Kinase II and Glutamate Release at Rat 
      Cerebrocortical Nerve Terminals.
PG  - 630-636
LID - 10.4062/biomolther.2021.046 [doi]
AB  - Eupafolin, a constituent of the aerial parts of Phyla nodiflora, has 
      neuroprotective property. Because reducing the synaptic release of glutamate is 
      crucial to achieving pharmacotherapeutic effects of neuroprotectants, we 
      investigated the effect of eupafolin on glutamate release in rat cerebrocortical 
      synaptosomes and explored the possible mechanism. We discovered that eupafolin 
      depressed 4-aminopyridine (4-AP)-induced glutamate release, and this phenomenon 
      was prevented in the absence of extracellular calcium. Eupafolin inhibition of 
      glutamate release from synaptic vesicles was confirmed through measurement of the 
      release of the fluorescent dye FM 1-43. Eupafolin decreased 4-AP-induced 
      [Ca(2+)](i) elevation and had no effect on synaptosomal membrane potential. The 
      inhibition of P/Q-type Ca(2+) channels reduced the decrease in glutamate release 
      that was caused by eupafolin, and docking data revealed that eupafolin interacted 
      with P/Q-type Ca(2+) channels. Additionally, the inhibition of 
      calcium/calmodulindependent protein kinase II (CaMKII) prevented the effect of 
      eupafolin on evoked glutamate release. Eupafolin also reduced the 4-AP-induced 
      activation of CaMK II and the subsequent phosphorylation of synapsin I, which is 
      the main presynaptic target of CaMKII. Therefore, eupafolin suppresses P/Q-type 
      Ca(2+) channels and thereby inhibits CaMKII/synapsin I pathways and the release 
      of glutamate from rat cerebrocortical synaptosomes.
FAU - Chang, Anna
AU  - Chang A
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
AD  - Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 22060, 
      Taiwan.
FAU - Hung, Chi-Feng
AU  - Hung CF
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
FAU - Hsieh, Pei-Wen
AU  - Hsieh PW
AD  - Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung 
      University of Science and Technology, Taoyuan 33303, Taiwan.
AD  - Graduate Institute of Natural Products, School of Traditional Chinese Medicine, 
      and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung 
      University, Taoyuan 33303, Taiwan.
AD  - Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou 33305, Taiwan.
FAU - Ko, Horng-Huey
AU  - Ko HH
AD  - Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung 
      Medical University, Kaohsiung 80708, Taiwan.
AD  - Drug Development and Value Creation Center, Kaohsiung Medical University, 
      Kaohsiung 80708, Taiwan.
FAU - Wang, Su-Jane
AU  - Wang SJ
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
AD  - Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung 
      University of Science and Technology, Taoyuan 33303, Taiwan.
LA  - eng
PT  - Journal Article
PL  - Korea (South)
TA  - Biomol Ther (Seoul)
JT  - Biomolecules & therapeutics
JID - 101472832
PMC - PMC8551735
OTO - NOTNLM
OT  - CaMKII
OT  - Cerebrocortical synaptosomes
OT  - Eupafolin
OT  - Glutamate release
OT  - P/Q-type Ca2+ channels
OT  - Synapsin I
COIS- CONFLICT OF INTEREST The authors declare that they have no competing interests.
EDAT- 2021/09/04 06:00
MHDA- 2021/09/04 06:01
PMCR- 2021/09/03
CRDT- 2021/09/03 05:59
PHST- 2021/03/09 00:00 [received]
PHST- 2021/05/04 00:00 [revised]
PHST- 2021/05/28 00:00 [accepted]
PHST- 2021/09/04 06:00 [pubmed]
PHST- 2021/09/04 06:01 [medline]
PHST- 2021/09/03 05:59 [entrez]
PHST- 2021/09/03 00:00 [pmc-release]
AID - biomolther.2021.046 [pii]
AID - bt-29-6-630 [pii]
AID - 10.4062/biomolther.2021.046 [doi]
PST - ppublish
SO  - Biomol Ther (Seoul). 2021 Nov 1;29(6):630-636. doi: 10.4062/biomolther.2021.046.