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

English version

Autoři: Joo Hye Yeo ^aff001; Eun Ju Choi ^aff001; Jinu Lee ^aff001
Působiště autorů: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Songdogwahak-ro, Yeonsu-gu, Korea ^aff001
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222326

Souhrn

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 (Cx43) 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.

Klíčová slova:

Biology and life sciences – Biochemistry – Proteins – Post-translational modification – Phosphorylation – Luminescent proteins – Yellow fluorescent protein – Neurochemistry – Neurotransmitters – Biogenic amines – Catecholamines – Dopamine – Histamine – Hormones – Molecular biology – Molecular biology techniques – Molecular probe techniques – Immunoblotting – Neuroscience – Research and analysis methods – Medicine and health sciences – Diagnostic medicine – Signs and symptoms – Headaches – Migraine – Pathology and laboratory medicine – Pharmaceutics – Drug therapy – Receptor antagonist therapy – Calcium antagonist therapy – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Amines – Iodides – Organic chemistry

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

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