Histamine H1 receptor

The H₁ receptor is a histamine receptor, and thus an important target for clinically important drugs, and is likely one of the most important receptors for modulating mammalian circadian cycles.

Histamine H₁ receptor are metabotropic G-protein-coupled receptors expressed throughout the body, specifically 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) which activates phospholipase C and the phosphatidylinositol (PIP2) signalling pathway.

Role in inflammation

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

Neurophysiology

Histamine H₁ receptors are activated by endogenous histamine, which is released by neurons which have their cell bodies in the tuberomamillary 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 all together. It has been reported that histaminergic neurons have the most wake-selective firing pattern of all known neuronal types. [Passani, M. B., Lin, J. S., Hancock, A., Crochet, S., Blandina, P., 2004. The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders. Trends Pharmacol Sci 25, 618-625.]

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. [Reiner P. B., Kamondi A., 1994. Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current. Neuroscience 59(3), 579-88.]

See also

* Antihistamine – H₁-receptor antagonists

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Mitsuchashi M, Payan DG |title=Molecular and cellular analysis of histamine H1 receptors on cultured smooth muscle cells. |journal=J. Cell. Biochem. |volume=40 |issue= 2 |pages= 183–92 |year= 1989 |pmid= 2670975 |doi= 10.1002/jcb.240400207
*cite journal | author=Braman SS |title=Histamine receptors in the lung. |journal=N Engl Reg Allergy Proc |volume=8 |issue= 2 |pages= 116–20 |year= 1987 |pmid= 2886904 |doi=
*cite journal | author=Hill SJ, Ganellin CR, Timmerman H, "et al." |title=International Union of Pharmacology. XIII. Classification of histamine receptors. |journal=Pharmacol. Rev. |volume=49 |issue= 3 |pages= 253–78 |year= 1997 |pmid= 9311023 |doi=
*cite journal | author=Holden CA, Chan SC, Norris S, Hanifin JM |title=Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes. |journal=Agents Actions |volume=22 |issue= 1-2 |pages= 36–42 |year= 1988 |pmid= 2891264 |doi=
*cite journal | author=Moguilevsky N, Varsalona F, Noyer M, "et al." |title=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. |journal=Eur. J. Biochem. |volume=224 |issue= 2 |pages= 489–95 |year= 1994 |pmid= 7925364 |doi=
*cite journal | author=Fukui H, Fujimoto K, Mizuguchi H, "et al." |title=Molecular cloning of the human histamine H1 receptor gene. |journal=Biochem. Biophys. Res. Commun. |volume=201 |issue= 2 |pages= 894–901 |year= 1994 |pmid= 8003029 |doi= 10.1006/bbrc.1994.1786
*cite journal | author=Le Coniat M, Traiffort E, Ruat M, "et al." |title=Chromosomal localization of the human histamine H1-receptor gene. |journal=Hum. Genet. |volume=94 |issue= 2 |pages= 186–8 |year= 1994 |pmid= 8045566 |doi=
*cite journal | author=De Backer MD, Gommeren W, Moereels H, "et al." |title=Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor. |journal=Biochem. Biophys. Res. Commun. |volume=197 |issue= 3 |pages= 1601–8 |year= 1994 |pmid= 8280179 |doi=
*cite journal | author=Hishinuma S, Young JM |title=Characteristics of the binding of [3H] -mepyramine to intact human U373 MG astrocytoma cells: evidence for histamine-induced H1-receptor internalisation. |journal=Br. J. Pharmacol. |volume=116 |issue= 6 |pages= 2715–23 |year= 1996 |pmid= 8590995 |doi=
*cite journal | author=Max SI, Chowdhury BA, Fraser CM |title=Sequence analysis of the 5'-untranslated region of the human H1 histamine receptor-encoding gene. |journal=Gene |volume=171 |issue= 2 |pages= 309–10 |year= 1996 |pmid= 8666296 |doi=
*cite journal | author=De Backer MD, Loonen I, Verhasselt P, "et al." |title=Structure of the human histamine H1 receptor gene. |journal=Biochem. J. |volume=335 ( Pt 3) |issue= |pages= 663–70 |year= 1998 |pmid= 9794809 |doi=
*cite journal | author=Horváth BV, Szalai C, Mándi Y, "et al." |title=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. |journal=Immunol. Lett. |volume=70 |issue= 2 |pages= 95–9 |year= 1999 |pmid= 10569698 |doi=
*cite journal | author=Wang KY, Arima N, Higuchi S, "et al." |title=Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages. |journal=FEBS Lett. |volume=473 |issue= 3 |pages= 345–8 |year= 2000 |pmid= 10818238 |doi=
*cite journal | author=Oda T, Morikawa N, Saito Y, "et al." |title=Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. |journal=J. Biol. Chem. |volume=275 |issue= 47 |pages= 36781–6 |year= 2001 |pmid= 10973974 |doi= 10.1074/jbc.M006480200
*cite journal | author=Brew OB, Sullivan MH |title=Localisation of mRNAs for diamine oxidase and histamine receptors H1 and H2, at the feto-maternal interface of human pregnancy. |journal=Inflamm. Res. |volume=50 |issue= 9 |pages= 449–52 |year= 2002 |pmid= 11603849 |doi=
*cite journal | author=Gutzmer R, Langer K, Lisewski M, "et al." |title=Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells. |journal=J. Allergy Clin. Immunol. |volume=109 |issue= 3 |pages= 524–31 |year= 2002 |pmid= 11898002 |doi=
*cite journal | author=Idzko M, la Sala A, Ferrari D, "et al." |title=Expression and function of histamine receptors in human monocyte-derived dendritic cells. |journal=J. Allergy Clin. Immunol. |volume=109 |issue= 5 |pages= 839–46 |year= 2002 |pmid= 11994709 |doi=

External links

* [http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2303 IUPHAR GPCR Database - H₁ Histamine Receptor]

PBB_Controls
update_page = yes
require_manual_inspection = no
update_protein_box = yes
update_summary = no
update_citations = yes