The Mechanism of the Disruption of Mast Cells Produced by Compound 48/80¹

<jats:title>Summary.</jats:title><jats:p>The present studies were made on mast cells in the rat mesentery.</jats:p><jats:p>The disruption of mast cells by 48/80 was inhibited by various metal salts and other enzyme inhibitors.</jats:p><jats:p>Among numerous enzymes studied, only lecithinase A had the ability to disrupt mast cells. Trypsin, fibrinolysin, ribonuclease, hyaluronidase, etc. were inactive.</jats:p><jats:p>The disruptive action of lecithinase A was inhibited by the same agents which inhibited the action of 48/80.</jats:p><jats:p>The action of 48/80 was temperature‐dependent. It was inhibited below 20°C and above 45°—50°C. The inhibition above 45°—50°C was irreversible.</jats:p><jats:p>The effect of 48/80 was inhibited by incubation with acetic anhydride and 1,3‐diphosphoimidazole. The acetylation was not reserved under conditions which hydrolyzed phenyl acetate and thiol acetate. Dephosphorylation caused a disruption without the addition of a liberator.</jats:p><jats:p>Polyvalent immune serum against snake venom, “Antivenin”, and specific immune serum (from rabbits) against lecithinase A (from bee venom), blocked in high doses the disruptive action of both lecithinase A and of 48/80.</jats:p><jats:p>The observations are considered to support the hypothesis that 48/80 acts by activating a lytic anzyme attached to the mast cell mebrane. The activity of the enzyme is normally blocked by an inhibitor. When this inhibitor is removed, as by liberators such as 48/80, the enzyme becomes active and the membrane structures are attacked.</jats:p><jats:p>The implications of our mast cell enzyme theory for the histamine release produced by other releasers, for that occurring in anaphylactic reactions, etc., are discussed. Attention is drawn to the possible applicability of similar enzyme theories to biologically occurring and pharmacologically produced changes in membrane permeability.</jats:p>