Mechanism of histamine release induced by the ionophore X537A from isolated rat mast cells.

X537A released histamine from isolated histamine-retaining mast cell granules incubated at 37 degrees C in Tris-sodium (150 mM) or Tris-potassium (150 mM), but not in Tris-glucose (300 mM). The release was depressed at 0 degrees C. In contrast, decylamine released all histamine bound to the granules irrespective of the presence of monovalent cations in the incubation medium of temperature. X537A did not release histamine from an artificial heparin-protamine complex when incubated in deionized water. The mechanism of histamine release by X537A can be explained by the ability of the ionophore to carry monovalent cations across cellular membranes, hereby making the ions available for exchange with histamine bound to the granular matrix. This mechanism can be distinguished from that of agents triggering an exchange between cations and bound histamine through a calcium- and energy-dependent exocytotic process on the one hand and through membrane lysis on the other. Based on the observation that the ionophore was able to carry histamine into the bulk of an organic phase, various possibilities exist to explain how histamine escapes from the cells following release from intracellular granular stores.