Selective localization of histamine to electron dense granules in antigen-challenged sensitized rat mast cells and to similar granules isolated from sonicated mast cells. An electron microscope autoradiographic study.

The subcellular localization of histamine was studied in sensitized rat mast cells following antigen challenge and in granules obtained from sonicated cells, using an electron microscope autoradiographic technique. The mast cells were furnished with labelled histamine by incubation in 3-H-histidine. The silver grain distribution (reflecting the radioactive histamine) was highly non-random. The highest silver grain densities occured over homogeneous, electron dense (normal) granules and moderately electron dense granules. Swollen, less electron dense ("changed") granules with a reticular appearance and devoid of a limiting membrane had the lowest density of all subcellular structures studied and were therefore probably almost free of histamine. There was a good correlation between the percentage of electron dense granules, the histamine content and the silver grain density insaline-washed granule fractions isolated after sonication of mast cells for different times. These results support the hypothesis that histamine release occurs during the sequential exocytosis of storage granules, and during the sonication of mast cells, probably as a cation exchange between the amine, which is ionically bound to the heparin-protein complex of the granule matrix, and cations from the extracellular fluid. The exchanges will occur as soon as the perigranular membrane becomes premeable to water and cations.