Relationship of uptake of sodium and 45calcium to ATP-induced histamine release from rat mast cells

Histamine release from isolated rat mast cells induced by extracellular adenosine 5′‐triphosphate (ATP) in the presence of calcium was preceded by the uptake of sodium and 45 Ca in the cells. In contrast, the release induced by compound 48/80, n‐decylamine and chlorpromazine was not preceded by uptake of 45 Ca. Histamine release and 45 Ca uptake by ATP were completely inhibited by p ‐hydroxymercuribenzoate and incubation at 0°, whereas sodium uptake was partly reduced. In the presence of 2.5 mM‐CaCl 2 , ATP activated the uptake of 45 Ca whereas, as previously reported, no sodium uptake or histamine release occurred. All three effects of ATP were inhibited by MgCl 2 . Thus, under conditions where the uptake of either sodium or 45 Ca was inhibited, no histamine release was induced by extracellular ATP. Antimycin A did not inhibit ATP‐induced increase in membrane permeability for sodium and calcium but completely blocked the histamine release. It is concluded that for histamine release to be induced by extracellular ATP from rat mast cells, an increased cell membrane permeability for sodium and calcium is necessary but not in itself sufficient since the release reaction is also dependent on the metabolic state of the cells.