histamine H1 receptor

The H₁ receptor is a histamine receptor belonging to the family of rhodopsin-like G-protein-coupled receptors. This receptor is activated by the biogenic amine histamine. It is expressed in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system. The H₁ receptor is linked to an intracellular G-protein (G_q) that activates phospholipase C and the inositol triphosphate (IP3) signalling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. The crystal structure of the receptor has been determined (shown on the right/below){{cite journal | vauthors = Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S | title = Structure of the human histamine H1 receptor complex with doxepin | journal = Nature | volume = 475 | issue = 7354 | pages = 65–70 | date = June 2011 | pmid = 21697825 | pmc = 3131495 | doi = 10.1038/nature10236 }} and used to discover new histamine H₁ receptor ligands in structure-based virtual screening studies.{{cite journal | vauthors = de Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M, Iwata S, Shimamura T, Stevens RC, de Esch IJ, Leurs R | title = Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor | journal = Journal of Medicinal Chemistry | volume = 54 | issue = 23 | pages = 8195–8206 | date = December 2011 | pmid = 22007643 | pmc = 3228891 | doi = 10.1021/jm2011589 }}

Function

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.{{cite journal | vauthors = Canonica GW, Blaiss M | title = Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence | journal = The World Allergy Organization Journal | volume = 4 | issue = 2 | pages = 47–53 | date = February 2011 | pmid = 23268457 | pmc = 3500039 | doi = 10.1097/WOX.0b013e3182093e19 | quote = 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 }} H₁-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.

Histamine may play a role in penile erection.{{cite journal | vauthors = Cará AM, Lopes-Martins RA, Antunes E, Nahoum CR, De Nucci G | title = The role of histamine in human penile erection | journal = British Journal of Urology | volume = 75 | issue = 2 | pages = 220–224 | date = February 1995 | pmid = 7850330 | doi = 10.1111/j.1464-410x.1995.tb07315.x }}

==Neurophysiology==

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.{{cite journal | vauthors = Passani MB, Lin JS, Hancock A, Crochet S, Blandina P | title = The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders | journal = Trends in Pharmacological Sciences | volume = 25 | issue = 12 | pages = 618–625 | date = December 2004 | pmid = 15530639 | doi = 10.1016/j.tips.2004.10.003 }}

The tuberomammillary nucleus is a histaminergic nucleus that strongly regulates the sleep-wake cycle.{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 175–176 | edition = 2nd | chapter = Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin | quote = 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.}} 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|date=August 2018}}

SARS-CoV-2

A recent study published in August 2024 suggested that H1 receptor can act as an alternative entry point for the SARS-CoV-2 (COVID-19) 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.{{cite journal | vauthors = Yu F, Liu X, Ou H, Li X, Liu R, Lv X, Xiao S, Hu M, Liang T, Chen T, Wei X, Zhang Z, Liu S, Liu H, Zhu Y, Liu G, Tu T, Li P, Zhang H, Pan T, Ma X | title = The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2 | journal = mBio | volume = 15 | issue = 8 | pages = e0108824 | date = August 2024 | pmid = 38953634 | pmc = 11324024 | doi = 10.1128/mbio.01088-24 }}

References

External links

{{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2303 | title = Histamine Receptors: H₁ | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2006-07-20 | archive-date = 2016-03-03 | archive-url = https://web.archive.org/web/20160303192657/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2303 | url-status = dead }}

Category:Histamine receptors

histamine H1 receptor

Function

SARS-CoV-2

See also

References

Further reading

External links