The significance of mast cells as a source of histamine in the mouse brain.

Knowledge of the relative contributions of mast cells and neurons to the overall pool of histamine in the brain is a prerequisite to determining the significance and role of this amine in brain function. Consequently, we analyzed the levels of brain histamine in four genotypes (+/+, W/+, Wv/+, and W/Wv) of WBB6F1 mice, whose numbers of brain-associated mast cells vary in a genotypically specific manner. Although mast cell numbers ranged from a total absence of mast cells (W/Wv) to an average of about 500 mast cells/brain (W/+), no significant differences between genotypes were found in the quantities of histamine in whole brains, brain regions, or crude subcellular fractions. Thus, in this strain of mice, mast cells are not a significant source of histamine in the brain. This suggests that most of the histamine is of neuronal origin. Since neuronal histamine levels are maintained only by continued histidine decarboxylase activity, complete inhibition of this enzyme by alpha-fluoromethylhistidine, a "suicide" inhibitor of histidine decarboxylase, would totally deplete W/Wv mice of brain histamine. This was not found to occur in the W/Wv mice, suggesting that neuronal stores of histamine can be maintained in the absence of histidine decarboxylase, or that an additional nonneuronal, non-mast cell source of histamine exists in the W/Wv mouse brain.