Isradipine affects histamine-induced cytosolic Ca2+ movements in human endothelial cells.
Although endothelial actions of dihydropyridines remain controversial, isradipine has been observed to exert anti-atherosclerotic actions in which endothelium could be involved. This study was designed to investigate the direct effects of isradipine on cytosolic Ca2+ concentration in cultured human umbilical vein endothelial cells. Isradipine (from 10 nM to 1 microM) had no effect on unstimulated cells but dose-dependently decreased both the transient [Ca2+]i peak and the sustained increase induced by histamine. Its maximal effects were reached at 0.1 microM. In the absence of Ca2+ influx or in depolarized cells, 1 microM isradipine still significantly decreased the transient [Ca2+]i peak (by 23 +/- 8% and 42 +/- 11%). Ca2+ influx induced by re-establishment of transmembrane Ca2+ gradient was also inhibited by isradipine, as was that induced by 1 microM thapsigargin. These results demonstrate that isradipine is able to reduce both Ca2+ release from internal stores and the consequent Ca2+ entry in stimulated human endothelial cells.
Iouzalen
L
L
Department of Pharmacology, CNRS URA 1482, René Descartes University, Necker Medical School, Paris, France.
Devynck
M A
MA
David-Dufilho
M
M
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000187:drug effects*; D016257:Fura-2; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D017275:Isradipine / Q000494:pharmacology*; D013997:Time Factors; D014470:Umbilical Cord / Q000187:drug effects
D006632:Histamine; D002118:Calcium; D016257:Fura-2; D017275:Isradipine