Agents that Release Histamine from Mast Cells

A fully differentiated mast cell, packed with 500 to 1000 granules, poised for secretion, wants only the appropriate stimulus to release the contained histamine, heparin, and hydrolytic enzymes into the connective tissue. Since the major storage site of histamine in mammalian tissues was located in the mast cell by Riley & West (1), the cell has been a major focus in the study of histamine release. The literature is abundant and there is no dearth of reviews (2-7) and books (8-10) on the mast cell and its histamine-releasing activities. We concentrate in this review on agents of more or less known structure capable of releasing histamine, and attempt to collect information on a range of agents and to evaluate succinctly the available information on their modes of action. The behavior of mast cells in response to a few agents has been studied in considerable detail, and we stress these as archetypes. The important category of IgE-mediated release has recently been reviewed in this series (11) and elsewhere (12, 13) and will not be considered here. Under usual conditions, virtually all of the histamine stored in mast cells is located in the cells' secretory granules (14, 15, 16). These granules in the rat consist of a matrix of heparin and a limited number of proteins (17) of which only two, both mast cell proteases, have been characterized substan­ tially (18, 19). Histamine and several acid hydrolases are weakly associated with the matrix by ionic bonding (20, 21); some unbound histamine may