THE DELTA-ISOMER OF HEXACHLOROCYCLOHEXANE INDUCES RAPID RELEASE OF THE MYO-INOSITOL-1,4,5-TRISPHOSPHATE-SENSITIVE CA2-CELLS( STORE AND BLOCKS CAPACITATIVE CA2+ ENTRY IN RAT BASOPHILIC LEUKEMIA)

Antigenic stimulation of rat basophilic leukemia cells releases Ca2+ f rom internal stores and increases membrane permeability to Ca2+. The d elta isomer of hexachlorocyclohexane (delta-HCH) is structurally simil ar 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 m ediated 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) tra nsiently 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 o f cells with delta-HCH (25-100 mu M), but not lindane, leads to a prog ressive inhibition of the antigen- and thapsigargin-stimulated Ca2+ si gnal. Caffeine, a modulator of the ryanodine receptor Ca2+ channel, at tenuates the rise in intracellular Ca2+ induced by delta-HCH, suggesti ng that ryanodine receptor-like Ca2+ channels may be present in RBL ce lls. At 25 mu M delta-HCH, a concentration that does not inhibit the a ntigen-stimulated Ca2+ signal, the release of [H-3]serotonin from anti gen-stimulated cells is enhanced as is secretion of [H-3]serotonin fro m cells pretreated with 25-100 mu M lindane. The depletion of Ca2+ fro m intracellular stores by delta-HCH should evoke Ca2+ entry into the c ells by a capacitative mechanism; however, divalent cation permeabilit y across the plasma membrane (Mn2+ influx) is not increased but rather is decreased by delta-HCH. An understanding of the mechanism of actio n of delta-HCH in releasing stored Ca2+ and blocking Ca2+ influx acros s the plasma membrane may provide insights into the regulation of capa citative Ca2+ entry in nonexcitable cells.