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Korean J Physiol Pharmacol 2014; 18(2): 89-94

Published online April 28, 2014 https://doi.org/10.4196/kjpp.2014.18.2.89

Copyright © The Korean Journal of Physiology & Pharmacology.

DA-6034 Induces [Ca2+]i Increase in Epithelial Cells

Yu-Mi Yang1,*, Soonhong Park1,*, HyeWon Ji1, Tae-im Kim2, Eung Kweon Kim2, Kyung Koo Kang3, and Dong Min Shin1

1Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 120-752, 2Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 120-752, 3Research Institutes, Dong-A Pharmaceutical Company, Yongin 446-905, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca2+ signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca2+ signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca2+-activated Cl- channels (CaCCs) and increased intracellular calcium concentrations ([Ca2+]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca2+]i in mouse salivary gland cells and human corneal epithelial cells. [Ca2+]i increase of DA-6034 was dependent on the Ca2+ entry from extracellular and Ca2+ release from internal Ca2+ stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca2+ stores. These results suggest that DA-6034 induces Ca2+ signaling via extracellular Ca2+ entry and RyRs-sensitive Ca2+ release from internal Ca2+ stores in epithelial cells.

Keywords: Calcium signaling, DA-6034, Epithelial cells, Eupatilin