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:


Histamine receptors
Receptor Location Mechanism of action Function Antagonists Uses of antagonists
H1 Throughout the body, especially in:[6]
H2 Gs
H3 Gi
H4 Gi As of July 2021, 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.


  1. ^ Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, et al. (September 1997). "International Union of Pharmacology. XIII. Classification of histamine receptors". Pharmacological Reviews. 49 (3): 253–278. PMID 9311023.
  2. ^ Ravhe IS, Krishnan A, Manoj N (January 2021). "Evolutionary history of histamine receptors: Early vertebrate origin and expansion of the H3-H4 subtypes". Molecular Phylogenetics and Evolution. 154: 106989. doi:10.1016/j.ympev.2020.106989. PMID 33059072. S2CID 222842322.
  3. ^ a b Simons FE (November 2004). "Advances in H1-antihistamines". The New England Journal of Medicine. 351 (21): 2203–2217. doi:10.1056/NEJMra033121. PMID 15548781.S
  4. ^ Haas H, Panula P (February 2003). "The role of histamine and the tuberomamillary nucleus in the nervous system". Nature Reviews. Neuroscience. 4 (2): 121–130. doi:10.1038/nrn1034. PMID 12563283. S2CID 31148156.
  5. ^ Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S (November 2000). "Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes". The Journal of Biological Chemistry. 275 (47): 36781–36786. doi:10.1074/jbc.M006480200. PMID 10973974.
  6. ^ "Histamine H1 Receptor - an overview | ScienceDirect Topics". Retrieved 2023-10-03.
  7. ^ Deiteren A, De Man JG, Pelckmans PA, De Winter BY (March 2015). "Histamine H₄ receptors in the gastrointestinal tract". British Journal of Pharmacology. 172 (5): 1165–1178. doi:10.1111/bph.12989. PMC 4337694. PMID 25363289.
  8. ^ Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP (June 2003). "Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells". The Journal of Pharmacology and Experimental Therapeutics. 305 (3): 1212–1221. doi:10.1124/jpet.102.046581. PMID 12626656. S2CID 14932773.
  9. ^ "Histamine H4 Receptor Antagonist - an overview | ScienceDirect Topics". Retrieved 2023-10-03.
  10. ^ Kim KW, Kim BM, Lee KA, Lee SH, Firestein GS, Kim HR (April 2017). "Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid Arthritis". Scientific Reports. 7 (1): 1197. Bibcode:2017NatSR...7.1197K. doi:10.1038/s41598-017-01101-y. PMC 5430934. PMID 28446753.