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definitions - Histamine_H1_receptor

Histamine H1 Receptor Blockaders (n.)

1.(MeSH)Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.

Histamine H1 Receptor Antagonists (n.)

1.(MeSH)Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.

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Histamine H1 receptor

                   
Histamine receptor H1

Histamine H1 receptor in complex with doxepin(PDB entry 3RZE)
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HRH1; H1-R; hisH1
External IDs OMIM600167 MGI107619 HomoloGene668 IUPHAR: H1 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
Orthologs
Species Human Mouse
Entrez 3269 15465
Ensembl ENSG00000196639 ENSMUSG00000053004
UniProt P35367 P70174
RefSeq (mRNA) NM_000861.3 NM_001252642.1
RefSeq (protein) NP_000852.1 NP_001239571.1
Location (UCSC) Chr 3:
11.18 – 11.31 Mb
Chr 6:
114.35 – 114.43 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-allergic drugs. The crystal structure of the receptor has been determined (shown on the right).[1]

Contents

  Role in inflammation

The production of prostaglandin E2 synthase induces the release of histamine from neurons, causing systemic vasodilation, along with increased cell permeability due to its action on H1 receptors.

  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.[2]

In the cortex, activation of H1 receptors leads to inhibition of cell membrane potassium channels. This depolarizes the neurons and increases the resistance of the neuronal cell membrane, bringing the cell closer to its firing threshold and increasing the excitatory voltage produced by a given excitatory current. H1 receptor antagonists, or antihistamines, produce drowsiness because they oppose this action, reducing neuronal excitation.[3]

  See also

  References

  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. PMID 21697825. 
  2. ^ 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. 
  3. ^ Reiner PB, Kamondi A (April 1994). "Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current". Neuroscience 59 (3): 579–88. doi:10.1016/0306-4522(94)90178-3. PMID 8008209. 

  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. doi:10.1002/jcb.240400207. PMID 2670975. 
  • Braman SS (1987). "Histamine receptors in the lung.". N Engl Reg Allergy Proc 8 (2): 116–20. doi:10.2500/108854187778994446. PMID 2886904. 
  • Hill SJ, Ganellin CR, Timmerman H, et al. (1997). "International Union of Pharmacology. XIII. Classification of histamine receptors.". Pharmacol. Rev. 49 (3): 253–78. PMID 9311023. 
  • 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. doi:10.1007/BF01968814. PMID 2891264. 
  • 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. doi:10.1111/j.1432-1033.1994.00489.x. PMID 7925364. 
  • 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. doi:10.1006/bbrc.1994.1786. PMID 8003029. 
  • 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. PMID 8045566. 
  • 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. doi:10.1006/bbrc.1993.2662. PMID 8280179. 
  • 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. PMC 1909113. PMID 8590995. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1909113. 
  • 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. doi:10.1016/0378-1119(96)00036-4. PMID 8666296. 
  • De Backer MD, Loonen I, Verhasselt P, et al. (1998). "Structure of the human histamine H1 receptor gene". Biochem. J. 335 (3): 663–70. PMC 1219830. PMID 9794809. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1219830. 
  • 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. doi:10.1016/S0165-2478(99)00126-1. PMID 10569698. 
  • 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. doi:10.1016/S0014-5793(00)01560-X. PMID 10818238. 
  • 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. doi:10.1074/jbc.M006480200. PMID 10973974. 
  • 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. doi:10.1007/PL00000269. PMID 11603849. 
  • 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. doi:10.1067/mai.2002.121944. PMID 11898002. 
  • 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. doi:10.1067/mai.2002.124044. PMID 11994709. 

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