Molecular Biology of Histamine Systems 2.0

Dear Colleagues,

Histamine is arguably the most pleiotropic transmitter in the human body. Despite over a century of study since the first seminal work of Sr Henry Dale, who first identified an action for histamine on living tissue, and with significant advances in histamine pharmacology and drug development, with successful drug targeting three of the four histamine receptors, H₁-₄R, we are still lacking in a full understanding of the molecular biology of the histamine system. Histamine is synthesized from the amino acid histidine via the enzyme, histidine decarboxylase (HDC). The histamine receptors are classic G-protein coupled receptors. Major pharmacological heterogeneity between and within species has hindered the clinical development of H₃ and H₄R-targeted drugs. The pharmacological heterogeneity displayed by the histamine receptors are thought in part to be a result of alternative splicing which generates a number of possible splice variants, some of which have been shown to be functional and others which appear to be non-functional in terms of ligand binding and signal transduction. mRNA encoding the different isoforms has been shown to be distributed throughout the central nervous system in a region specific manner, but their relevance is yet to be established. Genetic polymorphisms have also been identified within the human receptor and HDC genes, some have been linked to disease. Despite the importance of histamine, transcriptional regulation of histamine receptor and HDC gene expression in mammals is still poorly understood. Furthermore, there are significant deficits in our knowledge regarding native histamine signaling pathways. This themed volume will endeavor to extend our understanding of these important issues.

Dr. Paul L. Chazot
Dr. Ilona Obara
Guest Editors

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