The delta 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.

Abstract

Antigenic stimulation of rat basophilic leukemia cells releases Ca2+ from internal stores and increases membrane permeability to Ca2+. The delta isomer of hexachlorocyclohexane (delta-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, delta-HCH and, to a lesser extent, lindane (gamma-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 delta-HCH (25-100 microM), 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 delta-HCH, suggesting that ryanodine receptor-like Ca2+ channels may be present in RBL cells. At 25 microM delta-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 microM lindane. The depletion of Ca2+ from intracellular stores by delta-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 delta-HCH. An understanding of the mechanism of action of delta-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.

• Authors: F C Mohr, S V Alojipan, S K Dunston, I N Pessah
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 48 Issue 3 Pg. 512-22 (Sep 1995) ISSN: 0026-895X [Print] United States
• PMID: 7565633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens
• Enzyme Inhibitors
• Terpenes
• Tritium
• delta-hexachlorocyclohexane
• Caffeine
• Manganese
• Hexachlorocyclohexane
• Thapsigargin
• Inositol 1,4,5-Trisphosphate
• Adenosine Triphosphate
• Calcium-Transporting ATPases
• Calcium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Antigens (pharmacology)
• Binding, Competitive
• Caffeine (pharmacology)
• Calcium (metabolism, pharmacokinetics, physiology)
• Calcium-Transporting ATPases (antagonists & inhibitors)
• Cell Membrane Permeability (drug effects)
• Endoplasmic Reticulum (metabolism)
• Enzyme Inhibitors (pharmacology)
• Hexachlorocyclohexane (metabolism, pharmacology)
• Inositol 1,4,5-Trisphosphate (metabolism)
• Intracellular Fluid (metabolism)
• Isomerism
• Leukemia, Basophilic, Acute (metabolism)
• Manganese (metabolism)
• Rats
• Sensitivity and Specificity
• Signal Transduction (drug effects, physiology)
• Stimulation, Chemical
• Terpenes (pharmacology)
• Thapsigargin
• Tritium
• Tumor Cells, Cultured (drug effects)