Histamine H1 receptor

Histamine H1 receptor

Histamine receptor H1
Histamine H1 receptor in complex with doxepin(PDB entry )
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; H1-R; H1R; HH1R; hisH1
External IDs IUPHAR: ChEMBL: GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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 1
  • Neurophysiology 2
  • See also 3
  • References 4
  • Further reading 5
  • External links 6

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.[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


  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".  
  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). receptor"1"Crystal structure-based virtual screening for fragment-like ligands of the human histamine H.  
  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. PMC 3500039. PMID 23268457. doi:10.1097/WOX.0b013e3182093e19. 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.  
  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.  

Further reading

  • Mitsuchashi M, Payan DG (1989). "Molecular and cellular analysis of histamine H1 receptors on cultured smooth muscle cells.". J. Cell. Biochem. 40 (2): 183–92.  
  • Braman SS (1987). "Histamine receptors in the lung.". N Engl Reg Allergy Proc 8 (2): 116–20.  
  • Hill SJ, Ganellin CR, Timmerman H, et al. (1997). "International Union of Pharmacology. XIII. Classification of histamine receptors.". Pharmacol. Rev. 49 (3): 253–78.  
  • Holden CA, Chan SC, Norris S, Hanifin JM (1988). "Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes.". Agents Actions 22 (1–2): 36–42.  
  • Moguilevsky N, Varsalona F, Noyer M, et al. (1994). "Stable expression of human H1-histamine-receptor cDNA in Chinese hamster ovary cells. Pharmacological characterisation of the protein, tissue distribution of messenger RNA and chromosomal localisation of the gene". Eur. J. Biochem. 224 (2): 489–95.  
  • Fukui H, Fujimoto K, Mizuguchi H, et al. (1994). "Molecular cloning of the human histamine H1 receptor gene". Biochem. Biophys. Res. Commun. 201 (2): 894–901.  
  • Le Coniat M, Traiffort E, Ruat M, et al. (1994). "Chromosomal localization of the human histamine H1-receptor gene". Hum. Genet. 94 (2): 186–8.  
  • De Backer MD, Gommeren W, Moereels H, et al. (1994). "Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor". Biochem. Biophys. Res. Commun. 197 (3): 1601–8.  
  • Hishinuma S, Young JM (1996). "Characteristics of the binding of [3H]-mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine-induced H1-receptor internalisation". Br. J. Pharmacol. 116 (6): 2715–23.  
  • Max SI, Chowdhury BA, Fraser CM (1996). "Sequence analysis of the 5'-untranslated region of the human H1 histamine receptor-encoding gene". Gene 171 (2): 309–10.  
  • De Backer MD, Loonen I, Verhasselt P, et al. (1998). "Structure of the human histamine H1 receptor gene". Biochem. J. 335 (3): 663–70.  
  • Horváth BV, Szalai C, Mándi Y, et al. (1999). "Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon gamma in peripheral human blood mononuclear cells and in CD19-depleted cell subsets". Immunol. Lett. 70 (2): 95–9.  
  • Wang KY, Arima N, Higuchi S, et al. (2000). "Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages". FEBS Lett. 473 (3): 345–8.  
  • Oda T, Morikawa N, Saito Y, et al. (2001). "Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes". J. Biol. Chem. 275 (47): 36781–6.  
  • Brew OB, Sullivan MH (2002). "Localisation of mRNAs for diamine oxidase and histamine receptors H1 and H2, at the feto-maternal interface of human pregnancy". Inflamm. Res. 50 (9): 449–52.  
  • Gutzmer R, Langer K, Lisewski M, et al. (2002). "Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells". J. Allergy Clin. Immunol. 109 (3): 524–31.  
  • Idzko M, la Sala A, Ferrari D, et al. (2002). "Expression and function of histamine receptors in human monocyte-derived dendritic cells". J. Allergy Clin. Immunol. 109 (5): 839–46.  

External links

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