Discharge of granules from isolated rat mast cells could be observed concomitantly with the histamine release from the cells when incubated with adenosine 5′-triphosphate (ATP) in the presence of Ca++. Since the percentage of mast cells with discharged granules was close to the percentage of histamine released, but the cells were still not emptied of granules, it is concluded that part of the histamine release occurred independently of granule discharge. In the absence of Ca++, only a slight histamine release occurred, and few extracellular granules were observed. ATP was shown to induce an immediate increase in the permeability of the cell membrane, as judged from the trypan blue exclusion test. ATP induced an increase in mast cell volume to more than twice the original volume, irrespective of the absence or presence of 0.25 mm Ca++, which is the optimum concentration for histamine release induced by ATP. By increasing the concentration of Ca++ in the incubation medium, the swelling effect of ATP on the cells was counteracted concomitantly with a decrease in the histamine release. It is concluded that swelling of the cells per se does not cause histamine release but is a necessary component for histamine release to occur from mast cells exposed to ATP and Ca++.
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Krüger et al. (2009) studied this question.