Terbinafine inhibits gap junctional intercellular communication

Toxicol Appl Pharmacol. 2016 Sep 15:307:102-107. doi: 10.1016/j.taap.2016.07.022. Epub 2016 Jul 31.

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.

Keywords: Gap junctional intercellular communication; I-YFP GJIC assay; Naftifine; Terbinafine.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Calcium / metabolism
  • Cell Communication / drug effects*
  • Cell Line
  • Cell Line, Tumor
  • Connexin 43 / genetics
  • Connexin 43 / metabolism
  • Dose-Response Relationship, Drug
  • Gap Junctions / drug effects*
  • Humans
  • Naphthalenes / pharmacology*
  • Terbinafine

Substances

  • Antifungal Agents
  • Connexin 43
  • Naphthalenes
  • Terbinafine
  • Calcium