Novel effect of carvedilol on Ca2+ movement in renal tubular cells

Chun Peng Liu, Hung Ting Chiang, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations

Abstract

The effect of carvedilol on intracellular free Ca2+ levels ([Ca2+]i) has not been explored previously. This study was aimed to examine the effect of carvedilol on Ca2+ handling in renal tubular cells. Madin-Darby canine kidney cells were used as a model for renal tubular cells and fura-2 was used as a fluorescent Ca2+ probe. Carvedilol increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 5μM. Extracellular Ca2+ removal partly inhibited the [Ca2+]i signals. Carvedilol-induced Ca2+ influx was verified by measuring Mn2+-induced quench of fura-2 fluorescence. Carvedilol-induced store Ca2+ release was reduced by pretreatment with 1μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) but not with 5μM ryanodine or 2μM carbonylcyanide m-chlorophenylhydrazone (a mitochondrial uncoupler). Carvedilol (30μM)-induced Ca2+ release was not affected by inhibiting phospholipase C with 1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-l)amino)hexyl)-1H-pyrrole- 2,5-dione (U73122; 2μM), but was potentiated by increasing cAMP levels or inhibiting protein kinase C. The carvedilol-induced Ca2+ mobilization was not significantly sequestered by the endoplasmic reticulum or mitochondria. This study shows that carvedilol increased [Ca2+]i in renal tubular cells by causing Ca2+ release from the endoplasmic reticulum and other unknown stores in an inositol-1,4,5-trisphosphate-independent manner, and by inducing Ca2+ influx. The Ca2+ release was modulated by cAMP and protein kinase C.

Original languageEnglish
Pages (from-to)1777-1784
Number of pages8
JournalBiochemical Pharmacology
Volume64
Issue number12
DOIs
StatePublished - 15 12 2002
Externally publishedYes

Keywords

  • Calcium
  • Carvedilol
  • Fura-2
  • MDCK cells
  • Renal
  • Thapsigargin

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