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Natural Product Isoliquiritigenin Activates GABAB Receptors to Decrease Voltage-Gate Ca2+ Channels and Glutamate Release in Rat Cerebrocortical Nerve Terminals
- Source :
- Biomolecules, Volume 11, Issue 10, Biomolecules, Vol 11, Iss 1537, p 1537 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- Reduction in glutamate release is a key mechanism for neuroprotection and we investigated the effect of isoliquiritigenin (ISL), an active ingredient of Glycyrrhiza with neuroprotective activities, on glutamate release in rat cerebrocortical nerve terminals (synaptosomes). ISL produced a concentration-dependent inhibition of glutamate release and reduced the intraterminal [Ca2+] increase. The inhibition of glutamate release by ISL was prevented after removing extracellular Ca2+ or blocking P/Q-type Ca2+ channels. This inhibition was mediated through the γ-aminobutyric acid type B (GABAB) receptors because ISL was unable to inhibit glutamate release in the presence of baclofen (an GABAB agonist) or CGP3548 (an GABAB antagonist) and docking data revealed that ISL interacted with GABAB receptors. Furthermore, the ISL inhibition of glutamate release was abolished through the inhibition of Gi/o-mediated responses or Gβγ subunits, but not by 8-bromoadenosine 3′,5′-cyclic monophosphate or adenylate cyclase inhibition. The ISL inhibition of glutamate release was also abolished through the inhibition of protein kinase C (PKC), and ISL decreased the phosphorylation of PKC. Thus, we inferred that ISL, through GABAB receptor activation and Gβγ-coupled inhibition of P/Q-type Ca2+ channels, suppressed the PKC phosphorylation to cause a decrease in evoked glutamate release at rat cerebrocortical nerve terminals.
- Subjects :
- Agonist
Baclofen
GABAB receptors
medicine.drug_class
Glutamic Acid
glutamate
GABAB receptor
Pharmacology
Microbiology
Biochemistry
Neuroprotection
Article
Gβγ
Calcium Channels, Q-Type
chemistry.chemical_compound
Chalcones
VGCCs
Glycyrrhiza
medicine
Animals
Humans
cerebrocortical synaptosomes
Receptor
Molecular Biology
Protein kinase C
Biological Products
Glutamate receptor
Calcium Channels, P-Type
QR1-502
Rats
isoliquiritigenin
Receptors, GABA-B
chemistry
nervous system
Calcium
GABA-B Receptor Antagonists
Isoliquiritigenin
Synaptosomes
Subjects
Details
- Language :
- English
- ISSN :
- 2218273X
- Database :
- OpenAIRE
- Journal :
- Biomolecules
- Accession number :
- edsair.doi.dedup.....2c60040a474ef9d1649c0789beabbed0
- Full Text :
- https://doi.org/10.3390/biom11101537