Mechanism of histamine secretion

Abstract

After the discovery in the fifties that the largest store of histamine in the body is located in the mast cells [1], the most important observation concerning histamine release has been that an enzymatic mechanism is involved and the release requires calcium and metabolic energy [2 5]. But very little was known about the metabolic parameters of the mast cells at lhal time. When it became possible to isolate the rat peritoneal mast cells as a pure population [6], the metabolic functions could be correlated with the secretory response. These studies not only confirnled energy dependence, but also showed that the secretion is associated with an increased energy requirement (see [7]). The biological role of calcium has been characterized in various cellular responses. Calcium is mobilized into the cytosol by influx across the plasma membrane or by release from intracellular slores. The importance of calcium in histamine release from mast cells was demonstrated by using the calcium ionophore A23187, which in tlle presence ol 'calcimn in the medium increases its influx [8]. In adrenal medullary cells, permeabilized by intense electric fields, which caused localized breakdown of the plasma membrane thus giving access of extracellular calcium to the cytosol, very low (btM) concentrations of calcium could induce catecholamine release [9]. Similar results have been obtained by permeabilizing mast cells with ATP [10] and Sendai virus [11]. In these preparations the extracellular calcium concentrations reflect those needed in the cytosol for exocytosis. The measurement of changes in the cytosol calcium concentration alone does not tell us the source of the calcium, whether by influx of extracetlular calcium or by release of intracellular stores. Optimal histamine release from sensitized mast cells challenged wilh the antigen is dependent on extracellular calcium. The polyamine, compound 48/80, on the other hand can release histamine in the absence of calcium in the medium.