Histamine Signaling in Allergic Disorders
Summary
Histamine is a biogenic amine released predominantly by mast cells and basophils during immediate hypersensitivity reactions. Four receptor subtypes (H1–H4) mediate its diverse effects, with the H1 receptor (H1R) orchestrating vasodilation, increased vascular permeability, smooth muscle contraction and sensory nerve activation that underpin pruritus, rhinorrhoea and bronchospasm in allergic rhinitis and asthma. Allergen-induced cross-linking of IgE on mast cells triggers degranulation and rapid histamine release. Binding to H1R activates Gq-protein signalling, phospholipase C and intracellular calcium flux, in turn engaging kinases such as protein kinase C and MAP kinases to modulate gene expression and receptor density. Chronic H1R signalling perpetuates inflammatory cell recruitment, tissue remodelling and neurogenic inflammation. Advances in understanding receptor desensitisation, biased agonism and receptor oligomerisation have informed the development of second-generation antihistamines with minimal central sedation and prolonged action. Investigations into H3R and H4R reveal modulatory roles in neuroimmune crosstalk, offering promising targets for refractory allergic conditions. Given the global rise in allergy prevalence and associated healthcare costs, precision modulation of histamine pathways remains a critical objective for next-generation therapeutics.
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Histamine Signaling in Allergic Disorders publication trend
The graph below shows the total number of articles in histamine signaling in allergic disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Histamine H1 receptor (H1R): Gq-protein-coupled receptor mediating vasodilation, permeability and smooth muscle contraction in allergic responses.
Protein kinase Cδ (PKCδ): Serine/threonine kinase isoform involved in intracellular signalling and gene regulation following receptor activation.
Extracellular signal-regulated kinase (ERK): MAP kinase family member transmitting signals from the cell surface to nuclear transcriptional machinery.
Mast cell: Granule-containing immune cell that releases histamine and other mediators upon allergen-induced activation.
Promoter: DNA region upstream of a gene that regulates its transcription initiation and expression level.
Antihistamine: Compound that blocks histamine receptors to alleviate allergic symptoms and inflammation.
References
- Involvement of Protein Kinase Cδ/Extracellular Signal-regulated Kinase/Poly(ADP-ribose) Polymerase-1 (PARP-1) Signaling Pathway in Histamine-induced Up-regulation of Histamine H1 Receptor Gene Expression in HeLa Cells*. Journal of Biological Chemistry (2011).
- Signaling Pathway of Histamine H1 Receptor-Mediated Histamine H1 Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells. Current Issues in Molecular Biology (2021).
- Evaluating the Anti-nociceptive and Anti-inflammatory Effects of Ketotifen and Fexofenadine in Rats. Advanced Pharmaceutical Bulletin (2015).
- Localization and Upregulation of the Nasal Histamine H1 Receptor in Perennial Allergic Rhinitis. Mediators of Inflammation (2012).
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