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.