Histamine Release from Isolated Rat Mast Cells in Metal Ion-Free Medium*

Abstract

It is generally recognized that the histamine release from mast cells induced by a number of histamine releasers including compound 48/80 or by antigen-antibody reaction is accompanied by extracellular discharge of granules (degranulation), though this is not always the case (1–3). Uvnäs and Thon (4, 5) proposed a hypothesis that the mechanism of histamine release from mast cells by compound 48/80 consists of two consecutive steps: the one being the process of extracellular discharge of granules, and the other, that occurs subsequently, a process of the release of histamine from extracellular granules. They consider that the first process is energy-requiring but the second one is a non-enzymatic simple ion exchange which occurs in the extracellular fluid phase between granular histamine and inorganic cations. This hypothesis is largely based on the following observations: 1) Mast cells which have degranulated in vitro on exposure to compound 48/80 retain their ability to store granules and histamine, and also to discharge granules and histamine on a second exposure to compound 48/80. 2) In an isotonic sucrose solution, granules are discharged from mast cells by compound 48/80 but histamine is not released; if these granules are resuspended in a medium containing inorganic cations, histamine release does occur. The first observation seems to be substantiated by recent findings of Diamant et al. (6) and Tasaka et al. (7) that when compound 48/80 is repeatedly applied topically to the surface of a single mast cell by means of microelectrophoresis, degranulation occurs in response to each application. We have failed to wholly reconfirm the latter observation, however, since in our experiment, histamine release from mast cells was produced to a considerable degree by compound 48/80 in isotonic sucrose solution, although an additional histamine release could be observed from mast cells resuspended in NaCl solution.