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)^[5] and used to discover new histamine H₁ receptor ligands in structure-based virtual screening studies.^[6]

HRH1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3RZE
Identifiers
Aliases	HRH1, H1-R, H1R, HH1R, hisH1, histamine receptor H1
External IDs	OMIM: 600167; MGI: 107619; HomoloGene: 668; GeneCards: HRH1; OMA:HRH1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p25.3 Start 11,137,093 bp[1] End 11,263,557 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 E3|6 53.05 cM Start 114,374,897 bp[2] End 114,460,257 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cartilage tissue tendon of biceps brachii Descending thoracic aorta Achilles tendon mucosa of urinary bladder synovial membrane ascending aorta synovial joint stromal cell of endometrium endothelial cell Top expressed in lumbar subsegment of spinal cord ventromedial nucleus supraoptic nucleus paraventricular nucleus of hypothalamus arcuate nucleus anterior amygdaloid area suprachiasmatic nucleus pontine nuclei dorsomedial hypothalamic nucleus medial dorsal nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function histamine receptor activity signal transducer activity G protein-coupled receptor activity G protein-coupled serotonin receptor activity neurotransmitter receptor activity Cellular component integral component of membrane membrane integral component of plasma membrane plasma membrane cytosol dendrite Biological process eosinophil chemotaxis inositol phosphate-mediated signaling regulation of vasoconstriction positive regulation of inositol trisphosphate biosynthetic process cellular response to histamine regulation of vascular permeability phospholipase C-activating G protein-coupled receptor signaling pathway regulation of synaptic plasticity G protein-coupled receptor signaling pathway modulation of chemical synaptic transmission inflammatory response visual learning signal transduction memory positive regulation of vasoconstriction G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger chemical synaptic transmission G protein-coupled serotonin receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3269 15465 Ensembl ENSG00000196639 ENSMUSG00000053004 UniProt P35367 P70174 RefSeq (mRNA) NM_000861 NM_001098211 NM_001098212 NM_001098213 NM_001252642 NM_001252643 NM_008285 NM_001317124 NM_001317125 NM_001317126 RefSeq (protein) NP_000852 NP_001091681 NP_001091682 NP_001091683 NP_001239571 NP_001239572 NP_001304053 NP_001304054 NP_001304055 NP_032311 Location (UCSC) Chr 3: 11.14 – 11.26 Mb Chr 6: 114.37 – 114.46 Mb PubMed search [3] [4]
Wikidata
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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.^[7] H₁-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.^[7]

Histamine may play a role in penile erection.^[8]

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.^[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

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.^[11]

See also

• Antihistamine – Histamine receptor antagonists
• H₁-receptor antagonist
• Histamine H₂-receptor
• Histamine H₃-receptor
• Histamine H₄-receptor