Inhibition of histamine release from rat mast cells by cytochalasin A and other sulfhydryl reagents

Abstract

We adduce several lines of evidence to indicate that the inhibition of histamine release from rat mast cells by cytochalasin A (Cyto A) depends on its reactivity with mast cell sulfhydryl (SH) groups: (1) Cyto A reacts with cysteine, glutathione and protein SH groups ; (2) prior reaction of Cyto A with glutathione eliminates its inhibitory action; and (3) 2,2'-dithiodipyridine (DTDP), a SH reagent with greater specificity for SH groups and very different structure from Cyto A, has parallel inhibitory effects on mast cell secretion. Inhibition of histamine release by Cyto A or by DTDP is independent of depression of cell ATP or cell glutathione. Inhibition of release induced by the calcium ionophore A23187 and polymyxin suggests that the two SH reagents act to block the release mechanism subsequent to a putative increase in cytoplasmic Ca 2+ concentration. In contrast, N(7-dimethylamino-4-methylcoumarinyl)maleimide (DACM), p-chloromercuri-benzene sulfonate (PCMBS) and N-ethylmaleimide (NEM) (< 10 −5 M) appear to react with a SH group required for polymyxin B but not A23187-induced release. The effect of NEM at high concentrations (5 × 10 −5 M) is attributable to depression of cell ATP.