Quantal corelease of histamine and 5-hydroxytryptamine from mast cells and the effects of prior incubation.

Corelease of histamine and 5-hydroxytryptamine from individual mast cells has been measured with fast-scan cyclic voltammetry using a carbon-fiber electrode placed next to a single cell. Release events, induced by exposure of the cells to the calcium ionophore, A23187, were resolved at the level of individual exocytotic events. Changes in the relative concentrations secreted from individual granules were observed after incubation with 5-hydroxytryptamine, histamine, and tryptophan. In contrast, an alteration in individual cell content after such incubations, analyzed with capillary chromatography, was only found after incubation with 5-hydroxytryptamine. Cells incubated with 5-hydroxytryptamine or its precursor, tryptophan, released more 5-hydroxytryptamine and less histamine per secretory event relative to controls. Coincubation of the cells with pargyline and 5-hydroxytryptamine further reduced the release of histamine. Since cell content of histamine is unchanged, the reduction in its release must be due to its displacement to a nonreleasable compartment induced by 5-hydroxytryptamine granular uptake. Incubation with histamine increased histamine secretion and, surprisingly, also increased 5-hydroxytryptamine release without changing its cell content. This result is consistent with a relaxation of the storage matrix accompanying histamine granular uptake allowing more 5-hydroxytryptamine to be released. These results demonstrate that the intragranular mode of storage as well as granular uptake of biogenic amines affects the stoichiometry of their release.