title: Terbinafine inhibits gap junctional intercellular communication.
abstract: Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca(2+) concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action.
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea. Electronic address: whitewndus@naver.com.
authors.forename: Ju Yeun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea; Department of Integrated OMICS for Biomedical Sciences, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea. Electronic address: sei_mee@naver.com.
authors.forename: Sei Mee
authors.initials: SM
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea. Electronic address: yureas@naver.com.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea. Electronic address: jinulee@yonsei.ac.kr.
authors.forename: Jinu
authors.initials: J
authors.lastname: Lee
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology*; D000077291:Terbinafine
chemical_list: D000935:Antifungal Agents; D018031:Connexin 43; D009281:Naphthalenes; D000077291:Terbinafine; D002118:Calcium
keywords: Gap junctional intercellular communication; I-YFP GJIC assay; Naftifine; Terbinafine