Histamine H1 receptor

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. 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.

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.

The tuberomammillary nucleus is a histaminergic nucleus that strongly regulates the sleep-wake cycle. 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.

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.

References

References

1. (June 2011). "Structure of the human histamine H1 receptor complex with doxepin". Nature.
2. (December 2011). "Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor". Journal of Medicinal Chemistry.
3. (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. (February 1995). "The role of histamine in human penile erection". British Journal of Urology.
5. (December 2004). "The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders". Trends in Pharmacological Sciences.
6. (2009). "Molecular Neuropharmacology: A Foundation for Clinical Neuroscience". McGraw-Hill Medical.
7. (August 2024). "The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2". mBio.