The δ isomer of hexachlorocyclohexane induces rapid release of the myo-Inositol-1,4,5-trisphosphate-sensitive Ca2+ store and blocks capacitative Ca2+ entry in rat basophilic leukemia cells

Frederick C Mohr, Sheila V. Alojipan, Sheryl K. Dunston, Isaac N Pessah

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Antigenic stimulation of rat basophilic leukemia cells releases Ca2+ from internal stores and increases membrane permeability to Ca2+. The δ isomer of hexachlorocyclohexane (δ-HCH) is structurally similar to myo-inositol-1,4,5-trisphosphate (IP3) and is a potent releaser of stored Ca2+ from permeabilized cells. This release of Ca2+ is not mediated by a competitive interaction with the IP3 receptor on the Ca2+ release channel on the endoplasmic reticulum. In intact cells, δ-HCH and, to a lesser extent, lindane (γ-hexachlorocyclohexane) transiently increase the intracellular Ca2+ concentration. The return to basal concentrations is mediated by the plasma membrane Ca2+ pumps and not by resequestration of Ca2+ into intracellular stores. Treatment of cells with δ-HCH (25-100 μM), but not lindane, leads to a progressive inhibition of the antigen- and thapsigargin-stimulated Ca2+ signal. Caffeine, a modulator of the ryanodine receptor Ca2+ channel, attenuates the rise in intracellular Ca2+ induced by δ-HCH, suggesting that ryanodine receptor-like Ca2+ channels may be present in RBL cells. At 25 μM δ-HCH, a concentration that does not inhibit the antigen-stimulated Ca2+ signal, the release of [3H]serotonin from antigen-stimulated cells is enhanced as is secretion of [3H]serotonin from cells pretreated with 25-100 μM lindane. The depletion of Ca2+ from intracellular stores by δ-HCH should evoke Ca2+ entry into the cells by a capacitative mechanism; however, divalent cation permeability across the plasma membrane (Mn2+ influx) is not increased but rather is decreased by δ-HCH. An understanding of the mechanism of action of δ-HCH in releasing stored Ca2+ and blocking Ca2+ influx across the plasma membrane may provide insights into the regulation of capacitative Ca2+ entry in nonexcitable cells.

Original languageEnglish (US)
Pages (from-to)512-522
Number of pages11
JournalMolecular Pharmacology
Volume48
Issue number3
StatePublished - Sep 1995

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'The δ isomer of hexachlorocyclohexane induces rapid release of the myo-Inositol-1,4,5-trisphosphate-sensitive Ca<sup>2+</sup> store and blocks capacitative Ca<sup>2+</sup> entry in rat basophilic leukemia cells'. Together they form a unique fingerprint.

  • Cite this