Ac. Redrup et al., FC(EPSILON)RI-MEDIATED CHLORIDE UPTAKE BY RAT MAST-CELLS - MODULATIONBY CHLORIDE TRANSPORT INHIBITORS IN RELATION TO HISTAMINE-SECRETION, British Journal of Pharmacology, 122(6), 1997, pp. 1188-1194
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.