Effect of Y-24180 on Ca2+ movement and proliferation in renal tubular cells

Yu Ying Chao, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)923-933
Number of pages11
JournalLife Sciences
Volume74
Issue number7
DOIs
StatePublished - 02 01 2004
Externally publishedYes

Keywords

  • Ca
  • Ca stores
  • Fura-2
  • MDCK cell
  • Renal tubular cell
  • Y-24180

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