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Molecular Biology of Histamine Systems 2024

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 1521

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Guest Editor
Department of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham DH1 3LE, UK
Interests: phytotherapy; phytochenistry; pharmacology; neuroscience; histamine; glutamate; behaviour; translation; validation; rational drug design; neuropathies
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Special Issue Information

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, histadine 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 signalling pathways. This themed volume will endeavour to extend our understanding of these important issues.

Prof. Dr. Paul L. Chazot
Guest Editor

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Keywords

  • histamine
  • molecular biology
  • genetics
  • mutations
  • disease
  • genomics
  • histamine signalling
  • synthesis
  • metabolism
  • isoforms
  • splicing
  • receptors
  • gene regulation
  • molecular structure
  • microbiome

Published Papers (1 paper)

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Research

16 pages, 3966 KiB  
Article
Histamine H1 Receptor-Mediated JNK Phosphorylation Is Regulated by Gq Protein-Dependent but Arrestin-Independent Pathways
by Shotaro Michinaga, Ayaka Nagata, Ryosuke Ogami, Yasuhiro Ogawa and Shigeru Hishinuma
Int. J. Mol. Sci. 2024, 25(6), 3395; https://doi.org/10.3390/ijms25063395 - 17 Mar 2024
Viewed by 519
Abstract
Arrestins are known to be involved not only in the desensitization and internalization of G protein-coupled receptors but also in the G protein-independent activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), to regulate cell [...] Read more.
Arrestins are known to be involved not only in the desensitization and internalization of G protein-coupled receptors but also in the G protein-independent activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), to regulate cell proliferation and inflammation. Our previous study revealed that the histamine H1 receptor-mediated activation of ERK is dually regulated by Gq proteins and arrestins. In this study, we investigated the roles of Gq proteins and arrestins in the H1 receptor-mediated activation of JNK in Chinese hamster ovary (CHO) cells expressing wild-type (WT) human H1 receptors, the Gq protein-biased mutant S487TR, and the arrestin-biased mutant S487A. In these mutants, the Ser487 residue in the C-terminus region of the WT was truncated (S487TR) or mutated to alanine (S487A). Histamine significantly stimulated JNK phosphorylation in CHO cells expressing WT and S487TR but not S487A. Histamine-induced JNK phosphorylation in CHO cells expressing WT and S487TR was suppressed by inhibitors against H1 receptors (ketotifen and diphenhydramine), Gq proteins (YM-254890), and protein kinase C (PKC) (GF109203X) as well as an intracellular Ca2+ chelator (BAPTA-AM) but not by inhibitors against G protein-coupled receptor kinases (GRK2/3) (cmpd101), β-arrestin2 (β-arrestin2 siRNA), and clathrin (hypertonic sucrose). These results suggest that the H1 receptor-mediated phosphorylation of JNK is regulated by Gq-protein/Ca2+/PKC-dependent but GRK/arrestin/clathrin-independent pathways. Full article
(This article belongs to the Special Issue Molecular Biology of Histamine Systems 2024)
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