FC(EPSILON)RI-MEDIATED CHLORIDE UPTAKE BY RAT MAST-CELLS - MODULATIONBY CHLORIDE TRANSPORT INHIBITORS IN RELATION TO HISTAMINE-SECRETION

1 We have examined the role of extracellular chloride in the mast cell secretion process. The immunologically-directed ligand, antibody to I gE (anti-IgE) required extracellular chloride ions for optimum secreti on from rat peritoneal mast cells. In contrast, replacement of extrace llular chloride did not alter the mast cell secretory response to comp ound 48/80, calcium ionaphore A23187 or substance P. 2 Anti-IgE-stimul ation of mast cells evoked a significant uptake of chloride ions compa red to nonstimulated cells. The magnitude of chloride uptake correlate d with the magnitude of stimulated histamine secretion. 3 Compound 48/ 80, substance P and A23187 did not alter the rate of chloride ion upta ke, although these agents caused significant histamine secretion. 4 Th e Na+/K+/2Cl(-) cotransport inhibitor, furosemide, reduced the rate of anti-IgE-stimulated chloride uptake at a relatively high concentratio n. (700 mu M) However, the more potent Na+/K+/2Cl(-) cotransport inhib itors, bumetanide (100 mu M) and piretanide (100 mu M) had no effect O n the stimulated chloride uptake. 5 Furosemide inhibited anti-IgE-indu ced histamine secretion, bumetanide potentiated the response and piret anide had no effect. This suggests that their respective action on his tamine secretion are unrelated to inhibition of the Na+/K+/2Cl(-) carr ier. 6 The chloride channel blocker, 5-nitro-2-((3-phenylpropyl)-amino )-benzoic acid (NPPB), reduced both anti-IgE-stimulated chloride uptak e and the corresponding histamine secretion ina dose-dependent manner. The magnitude of the inhibitory action of the drug on these two cellu lar processes was comparable, implying that chloride channel activity is related to the mechanism of histamine secretion. 7 It is concluded that chloride uptake has a role in the control of Fc(epsilon)RI-mediat ed histamine secretion from rodent mast cells.