In Vivo and In Vitro Evidence for Brain Uptake of 4-Phenylbutyrate by the Monocarboxylate Transporter 1 (MCT1)
DC Field | Value | Language |
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dc.contributor.author | Lee, Na-Young | - |
dc.contributor.author | Kang, Young-Sook | - |
dc.date.available | 2021-02-22T11:26:28Z | - |
dc.date.issued | 2016-07 | - |
dc.identifier.issn | 0724-8741 | - |
dc.identifier.issn | 1573-904X | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9718 | - |
dc.description.abstract | 4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for several neurodegenerative diseases. These activities require 4-PBA transport into the brain across the blood-brain barrier (BBB). The objective of the present study was to characterize the brain transport mechanism of 4-PBA through the BBB. The brain transport of 4-PBA across the BBB was investigated following intravenous (IV) injection and internal carotid artery perfusion (ICAP) in vivo. The mechanism of transport was examined using TR-BBB cells, an in vitro model of the BBB. The volume of distribution (V-D) of 4-PBA by rat brain was about 7-fold greater than that of sucrose, a BBB impermeable vascular space marker, suggesting the blood-to-brain transport of 4-PBA through the BBB in the physiological state. [C-14]4-PBA uptake by TR-BBB cells showed time-, pH- and concentration-dependence with a K (m) of 13.4 mM at pH 7.4 and 3.22 mM at pH 6.0. The uptake was Na+ independent, and was significantly inhibited by alpha-cyano-4-hydroxycinnamate (a typical inhibitor for monocarboxylate transport), endogenous monocarboxylate compounds and monocarboxylic drugs. Lactate and valproate competitively inhibited [C-14]4-PBA uptake with K (i) value of 13.5 mM and 7.47 mM, respectively. These results indicate the role of monocarboxylate transporters (MCTs) in 4-PBA transport into the brain at the BBB. TR-BBB cells expressed mRNA of rMCT1, 2, and 4, especially, rMCT1 showed high mRNA expression level. In addition, [C-14]4-PBA uptake was inhibited by rMCT1 specific small interfering RNA. The transport mechanism of 4-PBA from blood to brain across the BBB likely involves MCT1. | - |
dc.format.extent | 12 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | SPRINGER/PLENUM PUBLISHERS | - |
dc.title | In Vivo and In Vitro Evidence for Brain Uptake of 4-Phenylbutyrate by the Monocarboxylate Transporter 1 (MCT1) | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1007/s11095-016-1912-6 | - |
dc.identifier.scopusid | 2-s2.0-84962222910 | - |
dc.identifier.wosid | 000377615600015 | - |
dc.identifier.bibliographicCitation | PHARMACEUTICAL RESEARCH, v.33, no.7, pp 1711 - 1722 | - |
dc.citation.title | PHARMACEUTICAL RESEARCH | - |
dc.citation.volume | 33 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1711 | - |
dc.citation.endPage | 1722 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | CARRIER-MEDIATED TRANSPORT | - |
dc.subject.keywordPlus | NECROSIS-FACTOR-ALPHA | - |
dc.subject.keywordPlus | SODIUM PHENYLBUTYRATE | - |
dc.subject.keywordPlus | CACO-2 CELLS | - |
dc.subject.keywordPlus | PHARMACOLOGICAL STRATEGY | - |
dc.subject.keywordPlus | CHEMICAL CHAPERONES | - |
dc.subject.keywordPlus | TAURINE TRANSPORT | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | BARRIER | - |
dc.subject.keywordPlus | DRUG | - |
dc.subject.keywordAuthor | 4-Phenylbutyrate (4-PBA) | - |
dc.subject.keywordAuthor | blood-brain barrier | - |
dc.subject.keywordAuthor | drug transport | - |
dc.subject.keywordAuthor | internal carotid artery perfusion | - |
dc.subject.keywordAuthor | intravenous injection | - |
dc.subject.keywordAuthor | monocarboxylate transporter (MCT) | - |
dc.subject.keywordAuthor | TR-BBB cell | - |
dc.identifier.url | https://link.springer.com/article/10.1007%2Fs11095-016-1912-6 | - |
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