Figure 1. Histamine biosynthesis process and histamine receptors
distribution and induced effects.
In the brain, the tuberomamillary nucleus neurons is the main source of
histamine. Moreover, microglia also give rise to synthesize histamine,
while histamine produced from cerebrovascular endothelial cells is
controversial (shown in the middle). In the peripheral tissue, the mast
cells and basophils in the immune system common synthesize histamine.
Besides, the enterochromaffin-like cells in stomach also show the
possibility to synthesis histamine (shown in the left). L-histidine was
decarboxylated by HDC into histamine. Neuronal histamine was packaged
into vesicles VMAT-2, and calcium release evokes histamine release from
vesicles into the postsynaptic cleft, which is metabolized into
tele-methyhistamine by HNMT. There are 4 histamine receptors distributed
in the brain, post-synaptical H1R mediating neuronal excitation or
inhibition, post-synaptical H2R facilitating neuronal excitability, and
pre- or post- synaptical H3R inhibiting neuronal excitability, as well
the H4R exciting neurons which is not expressed in neurons.