alpha-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABA(A)-benzodiazepine Receptors
DC Field | Value | Language |
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dc.contributor.author | Yang, Hyejin | - |
dc.contributor.author | Woo, Junsung | - |
dc.contributor.author | Pae, Ae Nim | - |
dc.contributor.author | Um, Min Young | - |
dc.contributor.author | Cho, Nam-Chul | - |
dc.contributor.author | Park, Ki Duk | - |
dc.contributor.author | Yoon, Minseok | - |
dc.contributor.author | Kim, Jiyoung | - |
dc.contributor.author | Lee, C. Justin | - |
dc.contributor.author | Cho, Suengmok | - |
dc.date.accessioned | 2021-09-03T17:08:24Z | - |
dc.date.available | 2021-09-03T17:08:24Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2016-11-01 | - |
dc.identifier.issn | 0026-895X | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/86879 | - |
dc.description.abstract | alpha-Pinene is a major monoterpene of the pine tree essential oils. It has been reported that alpha-pinene shows anxiolytic and hypnotic effects upon inhaled administration. However, hypnotic effect by oral supplementation and the molecular mechanism of alpha-pinene have not been determined yet. By combining in vivo sleep behavior, ex vivo electrophysiological recording from brain slices, and in silico molecular modeling, we demonstrate that (2)-alpha-pinene shows sleep enhancing property through a direct binding to GABA(A)-benzodiazepine (BZD) receptors by acting as a partialmodulator at the BZDbinding site. The effect of (2)-alpha-pinene on sleep-wake profiles was evaluated by recording electroencephalogram and electromyogram. The molecular mechanism of (2)-alpha-pinene was investigated by electrophysiology and molecular docking study. (2)-alpha-pinene significantly increased the duration of non-rapid eye movement sleep (NREMS) and reduced the sleep latency by oral administration without affecting duration of rapid eye movement sleep and delta activity. (2)-alpha-pinene potentiated the GABA(A) receptor-mediated synaptic response by increasing the decay time constant of sIPSCs in hippocampal CA1 pyramidal neurons. These effects of (2)-alpha-pinene on sleep and inhibitory synaptic response were mimicked by zolpidem, acting as a modulator for GABA(A)-BZD receptors, and fully antagonized by flumazenil, an antagonist for GABA(A)-BZD receptor. (2)-alpha-pinene was found to bind to aromatic residues of alpha 1- and -gamma 2 subunits of GABA(A)-BZD receptors in the molecular model. We conclude that (2)-alpha-pinene enhances the quantity of NREMS without affecting the intensity of NREMS by prolonging GABAergic synaptic transmission, acting as a partial modulator of GABA(A)-BZD receptors and directly binding to the BZD binding site of GABA(A) receptor. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | - |
dc.subject | GABA-A RECEPTOR | - |
dc.subject | CHEMICAL-COMPOSITION | - |
dc.subject | BENZODIAZEPINE SITE | - |
dc.subject | ANTIOXIDANT ACTIVITY | - |
dc.subject | SUBUNIT | - |
dc.subject | NEEDLES | - |
dc.subject | BINDING | - |
dc.subject | (-)-ALPHA-PINENE | - |
dc.subject | MODULATION | - |
dc.subject | CHINA | - |
dc.title | alpha-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABA(A)-benzodiazepine Receptors | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, C. Justin | - |
dc.identifier.doi | 10.1124/mol.116.105080 | - |
dc.identifier.scopusid | 2-s2.0-84992697260 | - |
dc.identifier.wosid | 000388724800003 | - |
dc.identifier.bibliographicCitation | MOLECULAR PHARMACOLOGY, v.90, no.5, pp.530 - 539 | - |
dc.relation.isPartOf | MOLECULAR PHARMACOLOGY | - |
dc.citation.title | MOLECULAR PHARMACOLOGY | - |
dc.citation.volume | 90 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 530 | - |
dc.citation.endPage | 539 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | GABA-A RECEPTOR | - |
dc.subject.keywordPlus | CHEMICAL-COMPOSITION | - |
dc.subject.keywordPlus | BENZODIAZEPINE SITE | - |
dc.subject.keywordPlus | ANTIOXIDANT ACTIVITY | - |
dc.subject.keywordPlus | SUBUNIT | - |
dc.subject.keywordPlus | NEEDLES | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | (-)-ALPHA-PINENE | - |
dc.subject.keywordPlus | MODULATION | - |
dc.subject.keywordPlus | CHINA | - |
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