Abstract
Histamine plays important roles in the periphery such as vascular permeability, smooth muscle contraction, gastric acid secretion and other functions, and in the CNS as a waking amine. In this talk, I presented two topis; the mechanism of non-sedation of the second generation H1 blockers and L-histidine decarboxylase (HDC) (a histamine forming enzyme) gene knockout (KO) mice. In the former, by PET (positron emission tomography) techniques that clarified the distribution of the histamine H1 receptors in the living human brain with [11C] doxepin as a radioligand, the second generation H1 blockers are shown to be difficult in penetration through the blood brain barrier. In the latter, the penotypic analyses of HDC KO mice confirmed the roles assigned to histamine as described above, but also showed the involvement of the histamine systems in new functions such as angiogenesis, neutrophil and eosinophil recruits, bacterial exclusion, and others. The most remarkable findings are that the mast cells isolated from HDC-KO mice were fewer in number, smaller in size, and less dense in staining than those of wild-type mice, indicating that histamine is related to the proliferation and differentiation of mast cells.
