Editing Histamine receptor

{{short description|Class of receptor proteins that bind histamine}}

The '''histamine receptors''' are a class of [[G protein–coupled receptor]]s which bind [[histamine]] as their primary [[endogenous]] [[ligand]].<ref name="pmid9311023">{{cite journal | vauthors = Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL | display-authors = 6 | title = International Union of Pharmacology. XIII. Classification of histamine receptors | journal = Pharmacological Reviews | volume = 49 | issue = 3 | pages = 253–278 | date = September 1997 | pmid = 9311023 | url = http://pharmrev.aspetjournals.org/cgi/content/abstract/49/3/253 }}</ref><ref>{{cite journal | vauthors = Ravhe IS, Krishnan A, Manoj N | title = Evolutionary history of histamine receptors: Early vertebrate origin and expansion of the H<sub>3</sub>-H<sub>4</sub> subtypes | journal = Molecular Phylogenetics and Evolution | volume = 154 | pages = 106989 | date = January 2021 | pmid = 33059072 | doi = 10.1016/j.ympev.2020.106989 | s2cid = 222842322 }}</ref> Histamine is a [[neurotransmitter]] involved in various physiological processes. There are four main types of histamine receptors: H1, H2, H3, and H4. H1 receptors are linked to allergic responses, H2 to gastric acid regulation, H3 to neurotransmitter release modulation, and H4 to immune system function.

There are four known histamine receptors:
*[[histamine H1 receptor|H<sub>1</sub> receptor]]{{Dash}}Primarily located on [[Smooth muscle|smooth muscle cells]], endothelial cells, and neurons. Activation of H1 receptors mediates various responses, including smooth muscle contraction (leading to bronchoconstriction, intestinal cramping), increased vascular permeability (resulting in [[edema]]), and stimulation of sensory nerve endings (causing itching and pain). H1 antagonists, commonly known as antihistamines, are used to alleviate symptoms of allergies and allergic reactions.<ref name = "Simons_2004">{{cite journal | vauthors = Simons FE | title = Advances in H1-antihistamines | journal = The New England Journal of Medicine | volume = 351 | issue = 21 | pages = 2203–2217 | date = November 2004 | pmid = 15548781 | doi = 10.1056/NEJMra033121 }}S</ref>
*[[histamine H2 receptor|H<sub>2</sub> receptor]]{{Dash}}Found mainly in the stomach lining (parietal cells), H2 receptors regulate gastric acid secretion by stimulating the production of hydrochloric acid. H2 antagonists (H2 blockers) are used to reduce stomach acid production and treat conditions like [[gastroesophageal reflux disease]] (GERD) and peptic ulcers.<ref name = "Simons_2004" />
*[[histamine H3 receptor|H<sub>3</sub> receptor]]{{Dash}}Predominantly located in the central nervous system (CNS), particularly in regions associated with neurotransmitter release and modulation. H3 receptors act as presynaptic autoreceptors and heteroreceptors, regulating the release of neurotransmitters such as dopamine, serotonin, [[norepinephrine]], and acetylcholine. Modulation of H3 receptors is being explored as a potential target for various neurological and psychiatric disorders.<ref>{{cite journal | vauthors = Haas H, Panula P | title = The role of histamine and the tuberomamillary nucleus in the nervous system | journal = Nature Reviews. Neuroscience | volume = 4 | issue = 2 | pages = 121–130 | date = February 2003 | pmid = 12563283 | doi = 10.1038/nrn1034 | s2cid = 31148156 }}</ref>
*[[histamine H4 receptor|H<sub>4</sub> receptor]]{{Dash}}Initially discovered on immune cells, particularly mast cells, eosinophils, and T cells, H4 receptors are involved in immune responses, including [[chemotaxis]] (cellular movement in response to chemical signals) and cytokine production. These receptors play a role in inflammation and allergic reactions. Research on H4 receptors is ongoing to better understand their involvement in immune-related disorders and to develop potential therapeutic interventions.<ref>{{cite journal | vauthors = Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S | title = Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 47 | pages = 36781–36786 | date = November 2000 | pmid = 10973974 | doi = 10.1074/jbc.M006480200 | doi-access = free }}</ref>

==Comparison==
{| class="wikitable"
|+Histamine receptors
|-
! Receptor !! Location !! Mechanism of action !! Function !! Antagonists !! Uses of antagonists
|-
! [[Histamine H1 receptor|H<sub>1</sub>]]
| Throughout the body, especially in:<ref>{{Cite web |title=Histamine H1 Receptor - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/neuroscience/histamine-h1-receptor#:~:text=Histamine%20H1%20receptors%20are,heart,%20and%20central%20nervous%20system. |access-date=2023-10-03 |website=www.sciencedirect.com}}</ref> {{blist|[[Smooth muscle]]s|vascular [[endothelia]]l cells (cells of walls of blood vessels)|[[adrenal medulla]]|heart|brain|spinal cord}}
| [[Gq subunit|G<sub>q</sub>]]
|
*[[ileum]] contraction
*modulate [[circadian cycle]]
*itching
*[[systemic circulation|systemic]] [[vasodilatation]] (indirect effect throughout the increased production of [[Nitric oxide|NO]])
*[[bronchoconstriction]] (allergy-induced asthma)
|
*[[H1 antagonist|H<sub>1</sub>-receptor antagonist]]s
**[[Diphenhydramine]]
**[[Loratadine]]
**[[Cetirizine]]
**[[Fexofenadine]]
**[[Clemastine]]
**[[Rupatadine]]
| {{blist|[[Allergies]]|[[nausea]]|[[sleep disorder]]s}}
|-
! [[Histamine H2 receptor|H<sub>2</sub>]]
| {{blist|Gastric [[parietal cell]]s|smooth muscles|[[mast cell]]s|[[neutrophil]]s|heart|[[uterus]]}}
| [[gs subunit|G<sub>s</sub>]] <br> ↑ [[Cyclic adenosine monophosphate|cAMP<sup>2+</sup>]]
|
*speed up [[sinus rhythm]]
*Stimulation of [[gastric acid]] secretion
*[[Smooth muscle]] relaxation
*Inhibit [[antibody]] synthesis, [[T-cell]] proliferation and [[cytokine]] production
|
*[[H2 antagonist|H<sub>2</sub>-receptor antagonist]]s
**[[Ranitidine]]
**[[Cimetidine]]
**[[Famotidine]]
**[[Nizatidine]]
| {{blist|[[Peptic ulcer]] disease|[[Stress ulcer]]s|[[Gastroesophageal reflux disease]]|[[Dyspepsia]]|[[Aspiration pneumonia]]|[[Resistant schizophrenia]]}}
|-
! [[Histamine H3 receptor|H<sub>3</sub>]]
| {{blist|[[Thalamus]]|[[caudate nucleus]]|[[cerebral cortex]]|small intestine|testes|[[prostate]]}}
| [[gi subunit|G<sub>i</sub>]]
|
* Decrease Acetylcholine, Serotonin and Norepinephrine [[Neurotransmitter]] release in [[central nervous system|CNS]] 
* Presynaptic [[autoreceptor]]s
|
*[[H3 antagonist|H<sub>3</sub>-receptor antagonists]]
**[[ABT-239]]
**[[Ciproxifan]]
**[[Clobenpropit]]
**[[Thioperamide]]
| {{blist|[[Narcolepsy]]|[[Alzheimer's disease]]|[[Attention deficit hyperactivity disorder]] (ADHD)|[[Schizophrenia]]}}
|-
! [[Histamine H4 receptor|H<sub>4</sub>]]
|
*[[Immune system]]
**[[lymphocyte]]s
**[[leukocyte]]s
*[[Lymphoid organ]]s
*[[thymus]]
*[[spleen]]
*[[liver]]<ref>{{cite journal | vauthors = Deiteren A, De Man JG, Pelckmans PA, De Winter BY | title = Histamine H₄ receptors in the gastrointestinal tract | journal = British Journal of Pharmacology | volume = 172 | issue = 5 | pages = 1165–1178 | date = March 2015 | pmid = 25363289 | pmc = 4337694 | doi = 10.1111/bph.12989 }}</ref>
*[[gastrointestinal tract]] (GIT)
*[[pancreas]]
*[[bile duct]]s
| [[gi subunit|G<sub>i</sub>]]
|
*mediate [[mast cell]] [[chemotaxis]].<ref name="pmid12626656">{{cite journal | vauthors = Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP | title = Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 305 | issue = 3 | pages = 1212–1221 | date = June 2003 | pmid = 12626656 | doi = 10.1124/jpet.102.046581 | s2cid = 14932773 }}</ref> 
|
*[[H4 antagonist|H<sub>4</sub>-receptor antagonists]]
**[[Thioperamide]]
**[[JNJ 7777120]]
| {{As of|July 2021}}, no clinical uses exist.<br>Potential uses include:<ref>{{Cite web |title=Histamine H4 Receptor Antagonist - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/histamine-h4-receptor-antagonist#:~:text=Currently%20H4%20receptor%20antagonists%20have,inflammatory%20pain%20and%20neuropathic%20pain. |access-date=2023-10-03 |website=www.sciencedirect.com}}</ref> {{blist|[[rheumatoid arthritis]]<ref>{{cite journal | vauthors = Kim KW, Kim BM, Lee KA, Lee SH, Firestein GS, Kim HR | title = Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid Arthritis | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 1197 | date = April 2017 | pmid = 28446753 | pmc = 5430934 | doi = 10.1038/s41598-017-01101-y | bibcode = 2017NatSR...7.1197K }}</ref>|[[asthma]]|[[allergic rhinitis]]|[[atopic dermatitis]]|[[pruritus]]}}
|-
|}

There are several [[splice variant]]s of H<sub>3</sub> present in various [[species]]. Though all of the receptors are [[7-transmembrane]] [[g protein coupled receptor]]s, H<sub>1</sub> and H<sub>2</sub> are quite different from H<sub>3</sub> and H<sub>4</sub> in their activities. H<sub>1</sub> causes an increase in [[PIP2|PIP<sub>2</sub>]] [[hydrolysis]], H2 stimulates [[gastric acid]] secretion, and H3 mediates [[feedback inhibition]] of histamine.

== References ==
{{Reflist}}

== External links ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1287 | title = Histamine Receptors | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
*[https://web.archive.org/web/20131230231812/http://www.biotrend.com/download/5BT_Histamine_Review11_07.pdf Holger Stark: Histamine Receptors, BIOTREND Reviews No. 01, November 2007]
*{{usurped|1=[https://web.archive.org/web/20071010204900/http://macromoleculeinsights.com/histaminerec.php The Histamine Receptor]}}
* {{MeshName|Histamine+Receptor}}

{{G protein-coupled receptors}}
{{Histaminergics}}

[[Category:Integral membrane proteins]]
[[Category:Histamine receptors]]