TY - JOUR
T1 - Effect of Y-24180 on Ca2+ movement and proliferation in renal tubular cells
AU - Chao, Yu Ying
AU - Jan, Chung Ren
PY - 2004/1/2
Y1 - 2004/1/2
N2 - In canine renal tubular cells, the effect of Y-24180, a presumed specific platelet activating factor (PAF) receptor antagonist, on intracellular Ca 2+ concentration ([Ca2+]i) was measured by using fura-2 as a Ca2+-sensitive fluorescent probe. Y-24180 (0.1-10 μM) caused a rapid and sustained [Ca2+]i rise in a concentration-dependent manner. The [Ca2+]i rise was prevented by 30% by removal of extracellular Ca2+, but was not changed by dihydropyridines, verapamil and diltiazem. Y-24180-induced Ca 2+ influx was confirmed by Mn2+-influx induced quench of fura-2 fluorescence. 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 5 μM Y-24180 on [Ca2+]i was abolished; conversely, depletion of Ca2+ stores with 5 μM Y-24180 abolished thapsigargin-induced [Ca2+]i rise. U73122, an inhibitor of phoispholipase C, inhibited ATP-, but not Y-24180-induced [Ca 2+]i rise. Overnight treatment with Y-24180 did not alter cell proliferation rate. Collectively, these results suggest that Y-24180 acts as a potent, but not cytotoxic, Ca2+ mobilizer in renal tubular cells, by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release. Since alterations in Ca2+ movement may interfere many cellular signaling processes unrelated to modulation of PAF receptors, caution must be applied in using this chemical as a selective PAF receptor antagonist.
AB - In canine renal tubular cells, the effect of Y-24180, a presumed specific platelet activating factor (PAF) receptor antagonist, on intracellular Ca 2+ concentration ([Ca2+]i) was measured by using fura-2 as a Ca2+-sensitive fluorescent probe. Y-24180 (0.1-10 μM) caused a rapid and sustained [Ca2+]i rise in a concentration-dependent manner. The [Ca2+]i rise was prevented by 30% by removal of extracellular Ca2+, but was not changed by dihydropyridines, verapamil and diltiazem. Y-24180-induced Ca 2+ influx was confirmed by Mn2+-influx induced quench of fura-2 fluorescence. 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 5 μM Y-24180 on [Ca2+]i was abolished; conversely, depletion of Ca2+ stores with 5 μM Y-24180 abolished thapsigargin-induced [Ca2+]i rise. U73122, an inhibitor of phoispholipase C, inhibited ATP-, but not Y-24180-induced [Ca 2+]i rise. Overnight treatment with Y-24180 did not alter cell proliferation rate. Collectively, these results suggest that Y-24180 acts as a potent, but not cytotoxic, Ca2+ mobilizer in renal tubular cells, by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release. Since alterations in Ca2+ movement may interfere many cellular signaling processes unrelated to modulation of PAF receptors, caution must be applied in using this chemical as a selective PAF receptor antagonist.
KW - Ca
KW - Ca stores
KW - Fura-2
KW - MDCK cell
KW - Renal tubular cell
KW - Y-24180
UR - http://www.scopus.com/inward/record.url?scp=0344196770&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2003.09.033
DO - 10.1016/j.lfs.2003.09.033
M3 - 文章
C2 - 14659980
AN - SCOPUS:0344196770
SN - 0024-3205
VL - 74
SP - 923
EP - 933
JO - Life Sciences
JF - Life Sciences
IS - 7
ER -