{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T03:00:46Z","timestamp":1774494046017,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology Taiwan","award":["MOST 109-2320-B-030-009"],"award-info":[{"award-number":["MOST 109-2320-B-030-009"]}]},{"name":"Far Eastern Memorial Hospital Taiwan","award":["109-FEMH-FJU-01"],"award-info":[{"award-number":["109-FEMH-FJU-01"]}]},{"name":"Far Eastern Memorial Hospital Taiwan","award":["FEMH-2021-C-007"],"award-info":[{"award-number":["FEMH-2021-C-007"]}]},{"name":"Far Eastern Memorial Hospital Taiwan","award":["FEMH-2021-C-010"],"award-info":[{"award-number":["FEMH-2021-C-010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 \u03b3-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 G\u03b2\u03b3 subunits, but not by 8-bromoadenosine 3\u2032,5\u2032-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 G\u03b2\u03b3-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.<\/jats:p>","DOI":"10.3390\/biom11101537","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T23:13:32Z","timestamp":1634598812000},"page":"1537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Natural Product Isoliquiritigenin Activates GABAB Receptors to Decrease Voltage-Gate Ca2+ Channels and Glutamate Release in Rat Cerebrocortical Nerve Terminals"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-5189","authenticated-orcid":false,"given":"Tzu-Yu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-3231","authenticated-orcid":false,"given":"Cheng-Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8882-4711","authenticated-orcid":false,"given":"Pei-Wen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan"},{"name":"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"},{"name":"Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7597-7655","authenticated-orcid":false,"given":"Kuan-Ming","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Cardiovascular Center, Far-Eastern Memorial Hospital, New Taipei 22060, Taiwan"},{"name":"Department of Nursing, Asia Eastern University of Science and Technology, New Taipei City 22060, Taiwan"},{"name":"Department of Photonics Engineering, Yuan Ze University, Taoyuan 32003, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7742-9508","authenticated-orcid":false,"given":"Ming-Yi","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Cardiovascular Center, Far-Eastern Memorial Hospital, New Taipei 22060, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-0259","authenticated-orcid":false,"given":"Su-Jane","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1002\/ptr.5348","article-title":"A Review: The Pharmacology of Isoliquiritigenin","volume":"29","author":"Peng","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3389\/fnagi.2018.00348","article-title":"Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models","volume":"10","author":"Ramalingam","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s00210-020-02030-w","article-title":"Isoliquiritigenin, an active ingredient of Glycyrrhiza, elicits antinociceptive effects via inhibition of Nav channels","volume":"394","author":"Miyamura","year":"2021","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.3892\/mmr.2015.3520","article-title":"Blood-brain barrier permeability of Gualou Guizhi granules and neuroprotective effects in ischemia\/reperfusion injury","volume":"12","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000495467","article-title":"Isoliquiritigenin Attenuates Neuroinflammation in Traumatic Brain Injury in Young Rats","volume":"26","author":"Liu","year":"2019","journal-title":"Neuroimmunomodulation"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhu, X., Liu, J., Chen, S., Xue, J., Huang, S., Wang, Y., and Chen, O. (2019). Isoliquiritigenin attenuates lipopolysaccharide-induced cognitive impairment through antioxidant and anti-inflammatory activity. BMC Neurosci., 20.","DOI":"10.1186\/s12868-019-0520-x"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.intimp.2019.04.028","article-title":"Neuroprotective effects of isoliquiritigenin against cognitive impairment via suppression of synaptic dysfunction, neuronal injury, and neuroinflammation in rats with kainic acid-induced seizures","volume":"72","author":"Zhu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.freeradbiomed.2020.03.016","article-title":"The antioxidant activity and neuroprotective mechanism of isoliquiritigenin","volume":"152","author":"Shi","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.bbrc.2012.04.053","article-title":"Isoliquiritigenin isolated from Glycyrrhiza uralensis protects neuronal cells against glutamate-induced mitochondrial dysfunction","volume":"421","author":"Yang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"127058","DOI":"10.1016\/j.bmcl.2020.127058","article-title":"Synthesis and biological evaluation of isoliquiritigenin derivatives as a neuroprotective agent against glutamate mediated neurotoxicity in HT22 cells","volume":"30","author":"Selvaraj","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12974-017-0895-5","article-title":"Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and\/or NF-\u03baB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway","volume":"14","author":"Zeng","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"638772","DOI":"10.3389\/fnins.2021.638772","article-title":"Isoliquiritigenin Confers Neuroprotection and Alleviates Amyloid-\u03b242-Induced Neuroinflammation in Microglia by Regulating the Nrf2\/NF-\u03baB Signaling","volume":"15","author":"Fu","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0165-6147(90)90116-P","article-title":"Excitatory amino acids and synaptic transmission: The evidence for a physiological function","volume":"11","author":"Headley","year":"1990","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/sj.mp.4001551","article-title":"Glutamate as a therapeutic target in psychiatric disorders","volume":"9","author":"Javitt","year":"2004","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0165-6147(90)90184-A","article-title":"Excitatory amino acid neurotoxicity and neurodegenerative disease","volume":"11","author":"Meldrum","year":"1990","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/aps.2009.24","article-title":"Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases","volume":"30","author":"Dong","year":"2009","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1111\/j.1460-9568.2007.05873.x","article-title":"Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca2+ signalling in hippocampal neurons","volume":"26","author":"Egea","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.neuropharm.2018.09.021","article-title":"Riluzole attenuates the efficacy of glutamatergic transmission by interfering with the size of the readily releasable neurotransmitter pool","volume":"143","author":"Lazarevic","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuro.2018.09.004","article-title":"Dexmedetomidine ameliorates lidocaine-induced spinal neurotoxicity via inhibiting glutamate release and the PKC pathway","volume":"69","author":"Xu","year":"2018","journal-title":"Neurotoxicology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2174\/1570159X17666191101125530","article-title":"Chinese Herbal Medicine Interventions in Neurological Disorder Therapeutics by Regulating Glutamate Signaling","volume":"18","author":"Liu","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9858","DOI":"10.1039\/D0FO02039G","article-title":"TCD, a triterpenoid isolated from wild bitter gourd, reduces synaptosomal release of glutamate and protects against kainic acid-induced neuronal death","volume":"11","author":"Hsu","year":"2020","journal-title":"Food Founction"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lu, C.W., Lin, T.Y., Chiu, K.M., Lee, M.Y., Huang, J.H., and Wang, S.J. (2020). Silymarin Inhibits Glutamate Release and Prevents against Kainic Acid-Induced Excitotoxic Injury in Rats. Biomedicines, 8.","DOI":"10.3390\/biomedicines8110486"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1007\/s12035-017-0515-5","article-title":"Attenuation of Glutamate-Induced Excitotoxicity by Withanolide-A in Neuron-Like Cells: Role for PI3K\/Akt\/MAPK Signaling Pathway","volume":"55","author":"Dar","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/321772a0","article-title":"Synaptosomes possess an exocytotic pool of glutamate","volume":"321","author":"Nicholls","year":"1986","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lu, C.W., Lin, T.Y., Huang, S.K., and Wang, S.J. (2016). Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca2+ Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071006"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wang, C.C., Hsieh, P.W., Kuo, J.R., and Wang, S.J. (2021). Rosmarinic Acid, a Bioactive Phenolic Compound, Inhibits Glutamate Release from Rat Cerebrocortical Synaptosomes through GABA(A) Receptor Activation. Biomolecules, 11.","DOI":"10.3390\/biom11071029"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1016\/S0021-9258(18)46043-7","article-title":"Localized Ca2+ entry preferentially effects protein dephosphorylation, phosphorylation, and glutamate release","volume":"267","author":"Sihra","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca2+ indicators with greatly improved fluorescence properties","volume":"260","author":"Grynkiewicz","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108451","DOI":"10.1016\/j.neuropharm.2021.108451","article-title":"Fingolimod inhibits glutamate release through activation of S1P1 receptors and the G protein \u03b2\u03b3 subunit-dependent pathway in rat cerebrocortical nerve terminals","volume":"185","author":"Wang","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejphar.2018.01.038","article-title":"Metabotropic glutamate 7 receptor agonist AMN082 inhibits glutamate release in rat cerebral cortex nerve terminal","volume":"823","author":"Wang","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0079-6123(08)60427-6","article-title":"Presynaptic modulation of glutamate release","volume":"116","author":"Nicholls","year":"1998","journal-title":"Prog. Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1111\/j.1471-4159.1991.tb08306.x","article-title":"An ion channel locus for the protein kinase C potentiation of transmitter glutamate release from guinea pig cerebrocortical synaptosomes","volume":"57","author":"Barrie","year":"1991","journal-title":"J. Neurochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/0014-5793(94)01061-7","article-title":"Phosphorylation of synapsin I and MARCKS in nerve terminals is mediated by Ca2+ entry via an Aga-GI sensitive Ca2+ channel which is coupled to glutamate exocytosis","volume":"353","author":"Coffey","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ejphar.2008.03.054","article-title":"Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABAB receptor","volume":"587","author":"Jang","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1046\/j.1471-4159.1998.70041513.x","article-title":"Presynaptic GABAB receptor modulation of glutamate exocytosis from rat cerebrocortical nerve terminals: Receptor decoupling by protein kinase C","volume":"70","author":"Perkinton","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ejphar.2010.09.024","article-title":"GABAB receptors modulate depolarization-stimulated [\u00b3H] glutamate release in slices of the pars reticulata of the rat substantia nigra","volume":"649","author":"Paz","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Thomford, N.E., Senthebane, D.A., Rowe, A., Munro, D., Seele, P., Maroyi, A., and Dzobo, K. (2018). Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061578"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6336","DOI":"10.1021\/jm5018913","article-title":"Activation of the \u03b3-Aminobutyric Acid Type B (GABAB) Receptor by Agonists and Positive Allosteric Modulators","volume":"58","author":"Brown","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nature12725","article-title":"Structural mechanism of ligand activation in human GABAB receptor","volume":"504","author":"Geng","year":"2013","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1038\/s41380-020-0709-5","article-title":"Binding of clozapine to the GABAB receptor: Clinical and structural insights","volume":"25","author":"Nair","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S1054-3589(10)58006-2","article-title":"GABAB receptor coupling to G-proteins and ion channels","volume":"58","author":"Padgett","year":"2010","journal-title":"Adv. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev.pa.33.040193.001221","article-title":"Covalent modifications of G-proteins","volume":"32","author":"Yamane","year":"1993","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/0028-3908(95)00133-Q","article-title":"Pharmacological characterization of presynaptic calcium channels using subsecond biochemical measurements of synaptosomal neurosecretion","volume":"34","author":"Turner","year":"1995","journal-title":"Neuropharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1111\/j.1460-9568.1997.tb01369.x","article-title":"Presynaptic modulation of glutamate release targets different calcium channels in rat cerebrocortical nerve terminals","volume":"9","year":"1997","journal-title":"Eur. J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0304-3940(02)00719-X","article-title":"Differential coupling of N- and P\/Q-type calcium channels to glutamate exocytosis in the rat cerebral cortex","volume":"330","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0166-2236(96)01015-6","article-title":"Presynaptic inhibition of elicited neurotransmitter release","volume":"20","author":"Wu","year":"1997","journal-title":"Trends Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jphs.2017.11.008","article-title":"The effect of ethanol extract of Glycyrrhiza uralensis on the voltage-gated sodium channel subtype 1.4","volume":"136","author":"Zhu","year":"2018","journal-title":"J. Pharmacol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1254\/jphs.08227FP","article-title":"Inhibitory effects of isoliquiritigenin and licorice extract on voltage-dependent K+ currents in H9c2 cells","volume":"108","author":"Noguchi","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1471-4159.1987.tb03393.x","article-title":"Calcium-dependent and -independent release of glutamate from synaptosomes monitored by continuous fluorometry","volume":"49","author":"Nicholls","year":"1987","journal-title":"J. Neurochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0896-6273(93)90145-H","article-title":"Nonvesicular release of neurotransmitter","volume":"11","author":"Attwell","year":"1993","journal-title":"Neuron"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1152\/physrev.00036.2003","article-title":"Molecular structure and physiological functions of GABAB receptors","volume":"84","author":"Bettler","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1113\/jphysiol.1995.sp020759","article-title":"GABAB receptor-mediated presynaptic inhibition in guinea-pig hippocampus is caused by reduction of presynaptic Ca2+ influx","volume":"485","author":"Wu","year":"1995","journal-title":"J. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1523\/JNEUROSCI.16-05-01623.1996","article-title":"Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse","volume":"16","author":"Dittman","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1523\/JNEUROSCI.18-09-03138.1998","article-title":"G-Protein-coupled modulation of presynaptic calcium currents and transmitter release by a GABAB receptor","volume":"18","author":"Takahashi","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8054","DOI":"10.1073\/pnas.141031298","article-title":"GTP-binding protein beta gamma subunits mediate presynaptic calcium current inhibition by GABAB receptor","volume":"98","author":"Kajikawa","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1074\/jbc.TM118.004163","article-title":"The expanding roles and mechanisms of G protein-mediated presynaptic inhibition","volume":"294","author":"Zurawski","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/356618a0","article-title":"MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin","volume":"356","author":"Hartwig","year":"1992","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10538","DOI":"10.1074\/jbc.M211114200","article-title":"Phosphorylation of Munc18 by protein kinase C regulates the kinetics of exocytosis","volume":"278","author":"Barclay","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1042\/BST0331341","article-title":"Regulation of exocytosis by protein kinase C","volume":"33","author":"Morgan","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s10571-011-9722-1","article-title":"Isoliquiritigenin is a novel NMDA receptor antagonist in kampo medicine yokukansan","volume":"31","author":"Kawakami","year":"2011","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1093\/jn\/130.4.1007S","article-title":"Glutamate as a neurotransmitter in the brain: Review of physiology and pathology","volume":"130","author":"Meldrum","year":"2000","journal-title":"J. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s12272-012-0515-y","article-title":"Inhibitory effects of Glycyrrhizae radix and its active component, isoliquiritigenin, on A\u03b2 (25\u201335)-induced neurotoxicity in cultured rat cortical neurons","volume":"35","author":"Lee","year":"2012","journal-title":"Arch. Pharmacal Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/10\/1537\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:17:33Z","timestamp":1760167053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/10\/1537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,18]]},"references-count":62,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["biom11101537"],"URL":"https:\/\/doi.org\/10.3390\/biom11101537","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,18]]}}}