Regulation of mammalian histamine synthesis: Histidine decarboxylase

Histamine plays a wide variety of physiological and pathological responses, such as immediate allergy, inflammation, gastric acid secretion, neurotransmission, and immune modulation. Histamine synthesis is mediated by the enzyme, L-histidine decarboxylase (HDC), which catalyzes decarboxylation of L-histidine. In contrast to extensive investigation and development of specific antagonists for histamine receptors, regulation of histamine synthesis remains to be clarified. We review here a series of studies about regulation of histamine synthesis, with a particular attention to the rate-limiting enzyme, HDC. We describe and discuss about the findings on various aspects of HDC, such as transcriptional regulation, post-translational regulation, and novel functions identified with the gene targeted mouse strain for HDC. It should be surely required for better understanding of the physiological roles of histamine to clarify the regulation of histamine synthesis, since accumulating evidence has indicated the critical roles of newly-formed histamine in health and disease.