Inhibition of gap junctional intercellular communication by an anti-migraine agent, flunarizine

Joo Hye Yeo, Eun Ju Choi, Jinu Lee

Research output: Contribution to journalArticle

Abstract

Gap junctions (GJs), which consist of proteins called connexins, are intercellular channels that allow the passage of ions, second messengers, and small molecules. GJs and connexins are considered as emerging therapeutic targets for various diseases. Previously, we screened numerous compounds using our recently developed iodide yellow fluorescent protein gap junctional intercellular communication (I-YFP GJIC) assay and found that flunarizine (FNZ), used for migraine prophylaxis and as an add-on therapy for epilepsy, inhibits GJIC in LN215 human glioma cells. In this study, we confirmed that FNZ inhibits GJIC using the I-YFP GJIC assay. We demonstrated that FNZ inhibits GJ activities via a mechanism that is independent of calcium channels and dopaminergic D2, histaminergic H1, or 5-HT receptors. In addition, we showed that FNZ significantly increases connexin 43 (C×43) phosphorylation on the cell surface, but does not alter the total amount of Cx43. The beneficial effects of FNZ on migraines and epilepsy might be related to GJ inhibition.

Original languageEnglish
Article numbere0222326
JournalPloS one
Volume14
Issue number9
DOIs
Publication statusPublished - 2019 Jan 1

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Flunarizine
migraine
cell communication
gap junctions
Migraine Disorders
connexins
Gap Junctions
epilepsy
Communication
iodides
Connexin 43
Connexins
Iodides
Epilepsy
Assays
therapeutics
calcium channels
second messengers
assays
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

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abstract = "Gap junctions (GJs), which consist of proteins called connexins, are intercellular channels that allow the passage of ions, second messengers, and small molecules. GJs and connexins are considered as emerging therapeutic targets for various diseases. Previously, we screened numerous compounds using our recently developed iodide yellow fluorescent protein gap junctional intercellular communication (I-YFP GJIC) assay and found that flunarizine (FNZ), used for migraine prophylaxis and as an add-on therapy for epilepsy, inhibits GJIC in LN215 human glioma cells. In this study, we confirmed that FNZ inhibits GJIC using the I-YFP GJIC assay. We demonstrated that FNZ inhibits GJ activities via a mechanism that is independent of calcium channels and dopaminergic D2, histaminergic H1, or 5-HT receptors. In addition, we showed that FNZ significantly increases connexin 43 (C×43) phosphorylation on the cell surface, but does not alter the total amount of Cx43. The beneficial effects of FNZ on migraines and epilepsy might be related to GJ inhibition.",
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Inhibition of gap junctional intercellular communication by an anti-migraine agent, flunarizine. / Yeo, Joo Hye; Choi, Eun Ju; Lee, Jinu.

In: PloS one, Vol. 14, No. 9, e0222326, 01.01.2019.

Research output: Contribution to journalArticle

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