Troglitazone inhibits the capacitative Ca2+ entry in endothelial cells.
To investigate the effects of troglitazone on the capacitative Ca2+ entry, we monitored changes in cytosolic Ca2+ concentrations ([Ca2+]i) induced by thapsigargin in fura-2-loaded porcine endothelial cells in situ and in primary culture. In aortic valve endothelial cells in situ, thapsigargin induced sustained elevation of [Ca2+]i. Both troglitazone and SKF 96365 inhibited the steady state increase in [Ca2+]i in a concentration-dependent manner. At 30 microM, troglitazone and SKF 96365 inhibited the [Ca2+]i elevation to 19.4 +/- 3.6% and 43.9 +/- 4.5%, respectively. In aortic endothelial cells in primary culture, both troglitazone (10 microM) and SKF 96365 (100 microM) completely inhibited the thapsigargin-induced [Ca2+]i increase. The EC50 value of troglitazone (1.4 +/- 0.1 microM) was lower than that of SKF 96365 (10.0 +/- 3.3 microM). We suggest that troglitazone would be a useful tool to investigate the capacitative Ca2+ entry.
Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J
J
Kawasaki
K
K
Hirano
M
M
Hirano
J
J
Nishimura
M
M
Fujishima
H
H
Kanaide
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D013552:Swine; D019284:Thapsigargin / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D013997:Time Factors; D000077288:Troglitazone; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002839:Chromans; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013844:Thiazoles; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D004110:Diltiazem; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D000077288:Troglitazone; D001920:Bradykinin; D002118:Calcium