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

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. 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 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)^[1] and used to discover new histamine H₁ receptor ligands in structure-based virtual screening studies.^[2]

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]

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.^[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

• Antihistamine – H₁-receptor antagonists

References

1. Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (Jul 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 (Dec 2011). "Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor". Journal of Medicinal Chemistry 54 (23): 8195–206. doi:10.1021/jm2011589. PMC 3228891. PMID 22007643.
3. Canonica GW, Blaiss M (Feb 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 (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 (Dec 2004). "The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders". Trends in Pharmacological Sciences 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

• Mitsuchashi M, Payan DG (Jun 1989). "Molecular and cellular analysis of histamine H1 receptors on cultured smooth muscle cells". Journal of Cellular Biochemistry 40 (2): 183–92. doi:10.1002/jcb.240400207. PMID 2670975.
• Braman SS (1987). "Histamine receptors in the lung". New England and Regional Allergy Proceedings 8 (2): 116–20. doi:10.2500/108854187778994446. PMID 2886904.
• Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL (Sep 1997). "International Union of Pharmacology. XIII. Classification of histamine receptors". Pharmacological Reviews 49 (3): 253–78. PMID 9311023.
• Holden CA, Chan SC, Norris S, Hanifin JM (Oct 1987). "Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes". Agents and Actions 22 (1-2): 36–42. doi:10.1007/BF01968814. PMID 2891264.
• Moguilevsky N, Varsalona F, Noyer M, Gillard M, Guillaume JP, Garcia L, Szpirer C, Szpirer J, Bollen A (Sep 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". European Journal of Biochemistry / FEBS 224 (2): 489–95. doi:10.1111/j.1432-1033.1994.00489.x. PMID 7925364.
• Fukui H, Fujimoto K, Mizuguchi H, Sakamoto K, Horio Y, Takai S, Yamada K, Ito S (Jun 1994). "Molecular cloning of the human histamine H1 receptor gene". Biochemical and Biophysical Research Communications 201 (2): 894–901. doi:10.1006/bbrc.1994.1786. PMID 8003029.
• Le Coniat M, Traiffort E, Ruat M, Arrang JM, Berger R (Aug 1994). "Chromosomal localization of the human histamine H1-receptor gene". Human Genetics 94 (2): 186–8. doi:10.1007/bf00202867. PMID 8045566.
• De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, Luyten WH (Dec 1993). "Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor". Biochemical and Biophysical Research Communications 197 (3): 1601–8. doi:10.1006/bbrc.1993.2662. PMID 8280179.
• Hishinuma S, Young JM (Nov 1995). "Characteristics of the binding of [3H]-mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine-induced H1-receptor internalisation". British Journal of Pharmacology 116 (6): 2715–23. doi:10.1111/j.1476-5381.1995.tb17232.x. PMC 1909113. PMID 8590995.
• Max SI, Chowdhury BA, Fraser CM (Jun 1996). "Sequence analysis of the 5'-untranslated region of the human H1 histamine receptor-encoding gene". Gene 171 (2): 309–10. doi:10.1016/0378-1119(96)00036-4. PMID 8666296.
• De Backer MD, Loonen I, Verhasselt P, Neefs JM, Luyten WH (Nov 1998). "Structure of the human histamine H1 receptor gene". The Biochemical Journal. 335 ( Pt 3) (3): 663–70. PMC 1219830. PMID 9794809.
• Horváth BV, Szalai C, Mándi Y, László V, Radvány Z, Darvas Z, Falus A (Nov 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". Immunology Letters 70 (2): 95–9. doi:10.1016/S0165-2478(99)00126-1. PMID 10569698.
• Wang KY, Arima N, Higuchi S, Shimajiri S, Tanimoto A, Murata Y, Hamada T, Sasaguri Y (May 2000). "Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages". FEBS Letters 473 (3): 345–8. doi:10.1016/S0014-5793(00)01560-X. PMID 10818238.
• Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S (Nov 2000). "Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes". The Journal of Biological Chemistry 275 (47): 36781–6. doi:10.1074/jbc.M006480200. PMID 10973974.
• Brew OB, Sullivan MH (Sep 2001). "Localisation of mRNAs for diamine oxidase and histamine receptors H1 and H2, at the feto-maternal interface of human pregnancy". Inflammation Research 50 (9): 449–52. doi:10.1007/PL00000269. PMID 11603849.
• Gutzmer R, Langer K, Lisewski M, Mommert S, Rieckborn D, Kapp A, Werfel T (Mar 2002). "Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells". The Journal of Allergy and Clinical Immunology 109 (3): 524–31. doi:10.1067/mai.2002.121944. PMID 11898002.
• Idzko M, la Sala A, Ferrari D, Panther E, Herouy Y, Dichmann S, Mockenhaupt M, Di Virgilio F, Girolomoni G, Norgauer J (May 2002). "Expression and function of histamine receptors in human monocyte-derived dendritic cells". The Journal of Allergy and Clinical Immunology 109 (5): 839–46. doi:10.1067/mai.2002.124044. PMID 11994709.

External links

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