Effects of microfilament-active drugs, phalloidin and the cytochalasins A and B, on exocytosis in mast cells evoked by 48/80 or A23187.

Rat peritoneal mast cells were used as a model system to study the effect, on exocytosis, of three agents known to interact with microfilaments. Mast cell secretion was evaluated by fluorimetric assay of histamine and by ruthenium red staining, the latter method allowing a direct visualization and quantitation of exocytosis at the light microscopic level. Phalloidin, in concentrations up to 300 microgram/ml, was without effect on either spontaneous or 48/80-evoked secretion, even after cells were exposed to the drug for 28 h. The failure of even high doses of phalloidin to influence cellular morphology and exocytosis in the mast cell may reflect the absence of a specific membrane receptor. Cytochalasin B was likewise without effect on the response to 48/80 in normally respiring cells; but inhibited this response in the presence of Antimycin A. This inhibitory effect probably reflects the ability of cytochalasin B to block glucose transport. In normally respiring cells, neither phalloidin nor cytochalasin B affected the active expulsion of granules from exocytotic pits. Cytochalasin A, without concomitant treatment with Antimycin A, completely inhibited secretion in response to both 48/80 and A23187, and did so in low concentration. Whether this striking inhibitory effect results from an interaction with microfilaments is uncertain for the inhibition could be mimicked by nonpenetrating thiol-oxidizing agents and prevented by impermeant thiol-protecting agents suggesting that cytochalasin A may inhibit histamine release by thiol-oxidation at the cell surface. Possible surface sulfhydryls are important for membrane rearrangements accompanying exocytosis.