Evidence for rapid histamine turnover and loss of histamine from immature rat mast cells.

Histamine synthetic activity which is high in young mast cells decreases as the cells mature [Beaven et al., J. Pharmac. exp. Ther. 224, 620 (1983)]. In this study we show that a substantial proportion of newly formed histamine in young mast cells leaked to the extracellular environment. The cells acquired the full ability to sequester newly formed histamine once the numbers of intracellular granules and the supply of sulfated mucopolysaccharide material within them had increased. Rat peritoneal mast cells were separated into successive fractions of increasing size and maturity by counter current elutriation. Loss of histamine from fractions of immature cells was demonstrated by a progressive accumulation of histamine in the medium without any decrease in intracellular histamine content. The estimated turnover time of histamine was less than 10 hr. In fractions of more mature cells, the proportion of cellular histamine released into the medium was substantially lower, giving estimated turnover times of 20 hr or longer. Studies with radiolabeled histidine also indicated that little, if any, newly formed histamine was lost from fractions of mature cells. Both release of endogenous histamine and formation of radiolabeled histamine from labeled histidine were inhibited by the histidine decarboxylase inhibitor alpha-fluoromethylhistidine (10 microM). Histamine turnover times were similar in the presence or absence of external histidine, a possible indication that the supply of intracellular histidine was sufficient to maintain normal histamine synthetic activity.