Volatile Anesthetic Effects on Inositol Trisphosphate-Gated Intracellular Calcium Stores in GH3 Cells

Alex S. Evers, M. Delawar Hossain

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3 Scopus citations


This chapter explores several studies to assess the effects of volatile anesthetic halothane on the inositol trisphosphate (IP3).signaling pathway in GH3 cells. To examine the effects of halothane on the proximal portions of the IP3 signaling pathway, GH3 cells have been labeled to equilibrium with [3H] inositol and stimulated with thyrotropin-releasing hormone (TRH) in the presence of 10 mM LiCl. Clinically relevant concentrations of halothane has minimal effects on resting [Ca2+]i in GH3 cells. The chapter indicates that high concentrations of halothane increase resting [Ca2+]i by releasing calcium from intracellular stores. TRH increases [Ca2+]i both by releasing sequestered calcium from intracellular stores and by stimulating influx through calcium channels. The maximum extent of inhibition of the [Ca2+]i response to TRH has been observed within 10 min of halothane administration and has been dependent on halothane concentration. Inhibition of the peak [Ca2+]i response to TRH could result from one of several mechanisms. Halothane could act by blocking IP3 binding or by inhibiting ion flux through the IP3 receptor/channel. Thapsigargin, such as halothane, inhibits the peak [Ca2+]i response to TRH. If halothane have been primarily acting to inhibit the Ca2+-ATPase, the combination of halothane and a saturating concentration of thapsigargin should produce the same exponential decay of the peak [Ca2+]i response to TRH as thapsigargin alone. The ability of halothane to increase the rate of leak calcium from intracellular stores provides an explanation for all the observed data. However various data indicate that anesthetic effects on IP3-releasable stores of calcium are not limited to halothane, other anesthetics such as isoflurane and octanol also produce effects similar to those observed with halothane.

Original languageEnglish
Pages (from-to)343-350
Number of pages8
JournalAdvances in Pharmacology
Issue numberC
StatePublished - Jan 1 1994


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