The expression of NF-κB, the transcription factor that regulates inflammatory processes, is promoted by the constitutive activity of the H1 receptor as well as by agonists that bind at the receptor.[7]H1-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.[7]
Histamine H1 receptors are activated by endogenous histamine, which is released by neurons that have their cell bodies in the tuberomammillary nucleus of the hypothalamus. The histaminergic neurons of the tuberomammillary nucleus become active during the 'wake' cycle, firing at approximately 2 Hz; during slow wave sleep, this firing rate drops to approximately 0.5 Hz. Finally, during REM sleep, histaminergic neurons stop firing altogether. It has been reported that histaminergic neurons have the most wake-selective firing pattern of all known neuronal types.[9]
The tuberomammillary nucleus is a histaminergic nucleus that strongly regulates the sleep-wake cycle.[10] H1-antihistamines that cross the blood–brain barrier inhibit H1 receptor activity on neurons that project from the tuberomammillary nucleus. This action is responsible for the drowsiness effect associated with these drugs.[citation needed]
SARS-CoV-2
According to recent study the histamine receptor H1 can act as an alternative entry point for the SARS-CoV-2 virus to infect cells, in addition to the main receptor ACE2. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2.
Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor.[11]
^ abCanonica GW, Blaiss M (February 2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". The World Allergy Organization Journal. 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC3500039. PMID23268457. The H1-receptor is a transmembrane protein belonging to the G-protein coupled receptor family. Signal transduction from the extracellular to the intracellular environment occurs as the GPCR becomes activated after binding of a specific ligand or agonist. A subunit of the G-protein subsequently dissociates and affects intracellular messaging including downstream signaling accomplished through various intermediaries such as cyclic AMP, cyclic GMP, calcium, and nuclear factor kappa B (NF-κB), a ubiquitous transcription factor thought to play an important role in immune-cell chemotaxis, proinflammatory cytokine production, expression of cell adhesion molecules, and other allergic and inflammatory conditions.1,8,12,30–32 ... For example, the H1-receptor promotes NF-κB in both a constitutive and agonist-dependent manner and all clinically available H1-antihistamines inhibit constitutive H1-receptor-mediated NF-κB production ... Importantly, because antihistamines can theoretically behave as inverse agonists or neutral antagonists, they are more properly described as H1-antihistamines rather than H1-receptor antagonists.15
^Cará AM, Lopes-Martins RA, Antunes E, Nahoum CR, De Nucci G (February 1995). "The role of histamine in human penile erection". British Journal of Urology. 75 (2): 220–224. doi:10.1111/j.1464-410x.1995.tb07315.x. PMID7850330.
^Passani MB, Lin JS, Hancock A, Crochet S, Blandina P (December 2004). "The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders". Trends in Pharmacological Sciences. 25 (12): 618–625. doi:10.1016/j.tips.2004.10.003. PMID15530639.
^Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 175–176. ISBN 9780071481274. Within the brain, histamine is synthesized exclusively by neurons with their cell bodies in the tuberomammillary nucleus (TMN) that lies within the posterior hypothalamus. There are approximately 64000 histaminergic neurons per side in humans. These cells project throughout the brain and spinal cord. Areas that receive especially dense projections include the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and hypothalamus. ... While the best characterized function of the histamine system in the brain is regulation of sleep and arousal, histamine is also involved in learning and memory ... It also appears that histamine is involved in the regulation of feeding and energy balance.
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De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, et al. (December 1993). "Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor". Biochemical and Biophysical Research Communications. 197 (3): 1601–1608. doi:10.1006/bbrc.1993.2662. PMID8280179.
Max SI, Chowdhury BA, Fraser CM (June 1996). "Sequence analysis of the 5'-untranslated region of the human H1 histamine receptor-encoding gene". Gene. 171 (2): 309–310. doi:10.1016/0378-1119(96)00036-4. PMID8666296.
Horváth BV, Szalai C, Mándi Y, László V, Radvány Z, Darvas Z, et al. (November 1999). "Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon gamma in peripheral human blood mononuclear cells and in CD19-depleted cell subsets". Immunology Letters. 70 (2): 95–99. doi:10.1016/S0165-2478(99)00126-1. PMID10569698.
Wang KY, Arima N, Higuchi S, Shimajiri S, Tanimoto A, Murata Y, et al. (May 2000). "Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages". FEBS Letters. 473 (3): 345–348. doi:10.1016/S0014-5793(00)01560-X. PMID10818238. S2CID772640.
Brew OB, Sullivan MH (September 2001). "Localisation of mRNAs for diamine oxidase and histamine receptors H1 and H2, at the feto-maternal interface of human pregnancy". Inflammation Research. 50 (9): 449–452. doi:10.1007/PL00000269. PMID11603849. S2CID28710647.
Gutzmer R, Langer K, Lisewski M, Mommert S, Rieckborn D, Kapp A, et al. (March 2002). "Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells". The Journal of Allergy and Clinical Immunology. 109 (3): 524–531. doi:10.1067/mai.2002.121944. PMID11898002.
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External links
"Histamine Receptors: H1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2006-07-20.
