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 ce lls 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 resol ved at the level of individual exocytotic events. Changes in the relat ive concentrations secreted from individual granules were observed aft er incubation with 5-hydroxytryptamine, histamine, and tryptophan, In contrast, an alteration in individual cell content after such incubati ons, analyzed with capillary chromatography, was only found after incu bation with 5-hydroxytryptamine. Cells incubated with 5-hydroxytryptam ine or its precursor, tryptophan, released more 5-hydroxytryptamine an d less histamine per secretory event relative to controls. Coincubtion of the cells with pargyline and 5-hydroxytryptamine further reduced t he release of histamine. Since cell content of histamine is unchanged. the reduction in its release must be due to its displacement to a non releasable compartment induced by 5-hydroxytryptamine granular uptake. Incubation with histamine increased histamine secretion and, surprisi ngly, also increased 5-hydroxytryptamine release without changing its cell content. This result is consistent with a relaxation of the stora ge matrix accompanying histamine granular uptake allowing more 5-hydro xytryptamine to be released. These results demonstrate that the intrag ranular mode of storage as well as granular uptake of biogenic amines affects the stoichiometry of their release.