Histamine H1 receptor

Histamine receptor H1
Histamine H1 receptor in complex with doxepin(PDB entry 3RZE)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3RZE
Identifiers
Symbols	HRH1 ; H1-R; H1R; HH1R; hisH1
External IDs	OMIM: 600167 MGI: 107619 HomoloGene: 668 IUPHAR: 262 ChEMBL: 231 GeneCards: HRH1 Gene
Gene ontology Molecular function • G-protein coupled receptor activity • histamine receptor activity • histamine binding Cellular component • nucleoplasm • cytoplasm • plasma membrane • integral component of plasma membrane Biological process • inflammatory response • G-protein coupled receptor signaling pathway • phospholipase C-activating G-protein coupled receptor signaling pathway • sensory perception of chemical stimulus • memory • visual learning • positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway • regulation of vasoconstriction • positive regulation of inositol trisphosphate biosynthetic process • regulation of vascular permeability • positive regulation of vasoconstriction • inositol phosphate-mediated signaling • regulation of synaptic plasticity • eosinophil chemotaxis • regulation of synaptic transmission • cellular response to histamine Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3269	15465
Ensembl	ENSG00000196639	ENSMUSG00000053004
UniProt	P35367	P70174
RefSeq (mRNA)	NM_000861	NM_001252642
RefSeq (protein)	NP_000852	NP_001239571
Location (UCSC)	Chr 3: 11.14 – 11.26 Mb	Chr 6: 114.4 – 114.48 Mb
PubMed search	[1]	[2]

The H₁ receptor is a histamine receptor belonging to the family of Rhodopsin-like G-protein-coupled receptors. This receptor, which is activated by the biogenic amine histamine, is expressed throughout the body, to be specific, 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 phosphatidylinositol (PIP2) 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) and used to discover new histamine H₁ receptor ligands in structure-based virtual screening studies.

Role in inflammation

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.

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.

See also

• Antihistamine – H₁-receptor antagonists