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 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.[citation needed]


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.[3]

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.[4]

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. ^ 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. 
  4. ^ 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[edit]

External links[edit]

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