KB-R7943 inhibits store-operated Ca(2+) entry in cultured neurons and astrocytes

Biochem Biophys Res Commun. 2000 Dec 20;279(2):354-7. doi: 10.1006/bbrc.2000.3968.

Abstract

We have studied cyclopiazonic acid (CPA)-sensitive store-operated Ca(2+) entry (SOCE) in cultured neurons and astrocytes and examined the effect of 2-[2-[4-(4-nitrobenzyloxy)phenyl]]isothiourea (KB-R7943), which is often used as a selective inhibitor of the Na(+)-Ca(2+) exchanger (NCX), on the SOCE. CPA increased transiently intracellular Ca(2+) concentration ([Ca(2+)](i)) followed by a sustained increase in [Ca(2+)](i) in neurons and astrocytes. The sustained increase in [Ca(2+)](i) depended on the presence of extracellular Ca(2+) and inhibited by SOCE inhibitors, but not by a Ca(2+) channel inhibitor. CPA also caused quenching of fura-2 fluorescence when the cells were incubated in Mn(2+)-containing medium. KB-R7943 at 10 microM inhibited significantly CPA-induced sustained increase in [Ca(2+)](i) in neurons and astrocytes. KB-R7943 also inhibited CPA-induced quenching of fura-2 fluorescence in the presence of extracellular Mn(2+). These results indicate that cultured neurons and astrocytes possess SOCE and that KB-R7943 inhibits not only NCX but also SOCE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Biological Transport / drug effects
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism*
  • Kinetics
  • Manganese / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Rats
  • Rats, Wistar
  • Sodium-Calcium Exchanger / antagonists & inhibitors*
  • Thiourea / analogs & derivatives*
  • Thiourea / pharmacology

Substances

  • 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
  • Calcium Channel Blockers
  • Sodium-Calcium Exchanger
  • Manganese
  • Thiourea
  • Calcium