Histamine receptor explained

The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand.^{[1] [2]}

Histamine receptors are proteins that bind with histamine, a neurotransmitter involved in various physiological processes. There are four main types: 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:

• H₁ receptor H1 Receptors: These receptors are primarily located on 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.^[3]
• H₂ receptor H2 Receptors: 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.
• H₃ receptor H3 Receptors: These receptors are 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.^[4]
• H₄ receptor H4 Receptors: 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.^[5]

Comparison

Histamine receptors

Receptor	Location	Mechanism of action	Function	Antagonists	Uses of antagonists
H1	Throughout the body, especially in:^[6]	Gq	ileum contraction modulate circadian cycle itching systemic vasodilatation (indirect effect throughout the increased production of NO) bronchoconstriction (allergy-induced asthma)	H1-receptor antagonists Azelastine Diphenhydramine Loratadine Cetirizine Fexofenadine Clemastine Rupatadine
H2		Gs ↑ cAMP^2+	speed up sinus rhythm Stimulation of gastric acid secretion Smooth muscle relaxation Inhibit antibody synthesis, T-cell proliferation and cytokine production	H2-receptor antagonists Ranitidine Cimetidine Famotidine Nizatidine
H3		Gi	Decrease Acetylcholine, Serotonin and Norepinephrine Neurotransmitter release in CNS Presynaptic autoreceptors	H3-receptor antagonists ABT-239 Ciproxifan Clobenpropit Thioperamide
H4	Immune system lymphocytes leukocytes Lymphoid organs thymus spleen liver^[7] gastrointestinal tract (GIT) pancreas bile ducts	Gi	mediate mast cell chemotaxis.^[8]	H4-receptor antagonists Thioperamide JNJ 7777120	, no clinical uses exist. Potential uses include:^[9]

There are several splice variants of H₃ present in various species. Though all of the receptors are 7-transmembrane g protein coupled receptors, H₁ and H₂ are quite different from H₃ and H₄ in their activities. H₁ causes an increase in PIP₂ hydrolysis, H2 stimulates gastric acid secretion, and H3 mediates feedback inhibition of histamine.

External links

• Web site: Histamine Receptors . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology .
• Holger Stark: Histamine Receptors, BIOTREND Reviews No. 01, November 2007
• The Histamine Receptor

Notes and References

1. Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL . 6 . International Union of Pharmacology. XIII. Classification of histamine receptors . Pharmacological Reviews . 49 . 3 . 253–278 . September 1997 . 9311023 .
2. Ravhe IS, Krishnan A, Manoj N . Evolutionary history of histamine receptors: Early vertebrate origin and expansion of the H₃-H₄ subtypes . Molecular Phylogenetics and Evolution . 154 . 106989 . January 2021 . 33059072 . 10.1016/j.ympev.2020.106989 . 222842322 .
3. Simons FE . Advances in H1-antihistamines . The New England Journal of Medicine . 351 . 21 . 2203–2217 . November 2004 . 15548781 . 10.1056/NEJMra033121 . S
4. Haas H, Panula P . The role of histamine and the tuberomamillary nucleus in the nervous system . Nature Reviews. Neuroscience . 4 . 2 . 121–130 . February 2003 . 12563283 . 10.1038/nrn1034 . 31148156 .
5. Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S . Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes . The Journal of Biological Chemistry . 275 . 47 . 36781–36786 . November 2000 . 10973974 . 10.1074/jbc.M006480200 . free .
6. Web site: Histamine H1 Receptor - an overview ScienceDirect Topics . 2023-10-03 . www.sciencedirect.com.
7. Deiteren A, De Man JG, Pelckmans PA, De Winter BY . Histamine H₄ receptors in the gastrointestinal tract . British Journal of Pharmacology . 172 . 5 . 1165–1178 . March 2015 . 25363289 . 4337694 . 10.1111/bph.12989 .
8. Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP . Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells . The Journal of Pharmacology and Experimental Therapeutics . 305 . 3 . 1212–1221 . June 2003 . 12626656 . 10.1124/jpet.102.046581 . 14932773 .
9. Web site: Histamine H4 Receptor Antagonist - an overview ScienceDirect Topics . 2023-10-03 . www.sciencedirect.com.