Histamine H1 receptor

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Histamine receptor H1
H1 Receptor with Doxepin.png
Histamine H1 receptor in complex with doxepin(PDB entry 3RZE)
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols HRH1 ; H1-R; H1R; HH1R; hisH1
External IDs OMIM600167 MGI107619 HomoloGene668 IUPHAR: 262 ChEMBL: 231 GeneCards: HRH1 Gene
RNA expression pattern
PBB GE HRH1 205579 at tn.png
PBB GE HRH1 205580 s at tn.png
More reference expression data
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 (Gq) that activates phospholipase C and the phosphatidylinositol (PIP2) signaling 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)[1] and used to discover new histamine H1 receptor ligands in structure-based virtual screening studies.[2]

Role in inflammation[edit]

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.[3] H1-antihistamines have been shown to attenuate NF-κB expression and mitigate certain inflammatory processes in associated cells.[3]


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.[4]

The tuberomammillary nucleus is a histaminergic nucleus that strongly regulates the sleep-wake cycle.[5] 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[edit]


  1. ^ Tatsuro Shimamura, Mitsunori Shiroishi, Simone Weyand, Hirokazu Tsujimoto, Graeme Winter, Vsevolod Katritch, Ruben Abagyan, Vadim Cherezov, Wei Liu, Gye Won Han, Takuya Kobayashi, Raymond C. Stevens & So Iwata (July 2011). "Structure of the human histamine H1 receptor complex with doxepin". Nature 475 (7354): 65–70. doi:10.1038/nature10236. PMC 3131495. PMID 21697825. 
  2. ^ de Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M, Iwata S, Shimamura T, Stevens RC, de Esch IJ, Leurs R (2011). "Crystal structure-based virtual screening for fragment-like ligands of the human histamine H1 receptor". J Med Chem 54 (23): 8195–8206. doi:10.1021/jm2011589. PMC 3228891. PMID 22007643. 
  3. ^ a b Canonica GW, Blaiss M (2011). "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". World Allergy Organ J 4 (2): 47–53. doi:10.1097/WOX.0b013e3182093e19. PMC 3500039. PMID 23268457. 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 GCPR 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
  4. ^ 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 Pharmacol. Sci. 25 (12): 618–25. doi:10.1016/j.tips.2004.10.003. PMID 15530639. 
  5. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. 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. 

Further reading[edit]

External links[edit]

  • "Histamine Receptors: H1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.