Effect of carvedilol on Ca2+ movement and cytotoxicity in human MG63 osteosarcoma cells

Basic & Clinical Pharmacology & Toxicology
Chun-Peng Liu, Chung-Ren Jan

Abstract

Carvedilol is a useful cardiovascular drug for treating heart failure, however, the in vitro effect on many cell types is unclear. In human MG63 osteosarcoma cells, the effect of carvedilol on intracellular Ca2+ concentrations ([Ca2+]i) and cytotoxicity was explored by using fura-2 and tetrazolium, respectively. Carvedilol at concentrations greater than 1 microM caused a rapid rise in [Ca2+]i in a concentration-dependent manner (EC50=15 microM). Carvedilol-induced [Ca2+]i rise was reduced by 60% by removal of extracellular Ca2+. Carvedilol-induced Mn2+-associated quench of intracellular fura-2 fluorescence also suggests that carvedilol induced extracellular Ca2+ influx. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic [Ca2+]i rise, after which the increasing effect of carvedilol on [Ca2+]i was inhibited by 50%. Conversely, pretreatment with carvedilol to deplete intracellular Ca2+ stores totally prevented thapsigargin from releasing more Ca2+. U73122, an inhibitor of phospholipase C, abolished histamine (an inositol 1,4,5-trisphosphate-dependent Ca2+ mobilizer)-induced, but not carvedilol-induced, [Ca2+]i rise. Pretreatment with phorbol 12-myristate 13-acetate and for...Continue Reading

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Citations

Oct 6, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Jin-Shiung ChengChung-Ren Jan
Feb 24, 2015·International Journal of Cardiology·Chin-Sheng LinChia-Hung Kao
May 20, 2008·Toxicology Letters·Hong-Tai ChangChung-Ren Jan
Dec 24, 2009·Human & Experimental Toxicology·Pochuen ShiehChung-Ren Jan
Jul 7, 2005·The Journal of Clinical Endocrinology and Metabolism·Ian R ReidAndrew B Grey
Sep 4, 2015·World Journal of Gastroenterology : WJG·Qian DingChun-Qing Zhang

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