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.
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.
Mohr
F C
FC
Department of Veterinary Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis 95616-8739, USA.
Alojipan
S V
SV
Dunston
S K
SK
Pessah
I N
IN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001667:Binding, Competitive; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002463:Cell Membrane Permeability / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D001556:Hexachlorocyclohexane / Q000378:metabolism / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D007536:Isomerism; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism; D051381:Rats; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000941:Antigens; D004791:Enzyme Inhibitors; D013729:Terpenes; D014316:Tritium; C086916:delta-hexachlorocyclohexane; D002110:Caffeine; D008345:Manganese; D001556:Hexachlorocyclohexane; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium