histamine h2 receptors


Summary: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)

Top Publications

  1. Jutel M, Watanabe T, Klunker S, Akdis M, Thomet O, Malolepszy J, et al. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature. 2001;413:420-5 pubmed
    ..These findings account for an important regulatory mechanism in the control of inflammatory functions through effector-cell-derived histamine. ..
  2. Szukiewicz D, Pyzlak M, Stangret A, Rongies W, Maslinska D. Decrease in expression of histamine H2 receptors by human amniotic epithelial cells during differentiation into pancreatic beta-like cells. Inflamm Res. 2010;59 Suppl 2:S205-7 pubmed publisher
    ..73 +/- 11.03 of the reference value obtained in control HAEC. Variable expression of H(2) during nicotinamide-induced differentiation of HAEC into PBLC may define a time-point, indicating involvement of histamine at the earlier stages. ..
  3. Orange P, Heath P, Wright S, Pearson R. Allelic variations of the human histamine H2 receptor gene. Neuroreport. 1996;7:1293-6 pubmed
    ..PCR amplification of human H2R gene fragments followed by cleavage with TaqI demonstrated the existence of allelic variation of the human H2R gene. ..
  4. Ezeamuzie C, Philips E. Histamine H(2) receptors mediate the inhibitory effect of histamine on human eosinophil degranulation. Br J Pharmacol. 2000;131:482-8 pubmed
    ..These results suggest that histamine, via stimulation of H(2) receptors and a consequent elevation of intracellular levels of cyclic AMP, inhibits human eosinophil degranulation. ..
  5. Kim J, Ogai A, Nakatani S, Hashimura K, Kanzaki H, Komamura K, et al. Impact of blockade of histamine H2 receptors on chronic heart failure revealed by retrospective and prospective randomized studies. J Am Coll Cardiol. 2006;48:1378-84 pubmed
    The goal of this work was to determine whether the blockade of histamine H2 receptors is beneficial for the pathophysiology of chronic heart failure (CHF)...
  6. Mancama D, Arranz M, Munro J, Osborne S, Makoff A, Collier D, et al. Investigation of promoter variants of the histamine 1 and 2 receptors in schizophrenia and clozapine response. Neurosci Lett. 2002;333:207-11 pubmed
  7. Smit M, Timmerman H, Alewijnse A, Punin M, van den Nieuwenhof I, Blauw J, et al. Visualization of agonist-induced internalization of histamine H2 receptors. Biochem Biophys Res Commun. 1995;214:1138-45 pubmed
    b>Histamine H2 receptors were tagged at the N-terminus with the eight amino acid Flag epitope to allow the immunological identification of the receptor peptide with the monoclonal anti-Flag M2 antibody...
  8. Asanuma H, Minamino T, Ogai A, Kim J, Asakura M, Komamura K, et al. Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs. J Mol Cell Cardiol. 2006;40:666-74 pubmed
    ..We conclude that the blockade of histamine H(2) receptors mediates improvements in the anaerobic myocardial metabolism, and thus protects against ischemia and reperfusion injury. ..
  9. Shayo C, Davio C, Brodsky A, Mladovan A, Legnazzi B, Rivera E, et al. Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937. Mol Pharmacol. 1997;51:983-90 pubmed

More Information


  1. Felix S, Baumann G, Niemczyk M, Ahmad Z, Hashemi T, Berdel W. Effects of platelet-activating factor on beta- and H2-receptor-mediated increase of myocardial contractile force in isolated perfused guinea pig hearts. Res Exp Med (Berl). 1991;191:1-9 pubmed
    ..35 nmol and 0.14 nmol, respectively, related to coronary flow rates of 1 ml/min) prior to PAF injection and 30 min after PAF.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  2. Orenstein S, Shalaby T, Kelsey S, Frankel E. Natural history of infant reflux esophagitis: symptoms and morphometric histology during one year without pharmacotherapy. Am J Gastroenterol. 2006;101:628-40 pubmed
    ..Although symptoms improved in more than half of the infants with reflux esophagitis followed longitudinally for 1 yr without pharmacotherapy, histology remained abnormal. ..
  3. Cabanie M, Godfraind T. The role of histamine in the cardiovascular system. Drugs Exp Clin Res. 1988;14:141-7 pubmed
  4. Takahashi H, Yoshida A, Iwagaki H, Yoshino T, Itoh H, Morichika T, et al. Histamine regulation of interleukin-18-initiating cytokine cascade is associated with down-regulation of intercellular adhesion molecule-1 expression in human peripheral blood mononuclear cells. J Pharmacol Exp Ther. 2002;300:227-35 pubmed
  5. Luo Y, Wang Y, Li N, Zheng T, Zhang L, She Y, et al. Actions of genistein on contractile response of smooth muscle isolated from guinea pig gallbladder. Hepatobiliary Pancreat Dis Int. 2009;8:614-9 pubmed
    ..Replacing traditional estrogen with phytoestrogen to treat menopause syndromes may increase the risk of gallstone formation. ..
  6. Shen B, Li H, Wang J. Excitatory effects of histamine on cerebellar interpositus nuclear cells of rats through H(2) receptors in vitro. Brain Res. 2002;948:64-71 pubmed
    ..The significance of the excitatory effect of histamine on the cerebellar nuclear cells is discussed. ..
  7. Orsini J, Spencer P. Effects of a histamine type 2 receptor antagonist, BMY-26539-01, on equine gastric acid secretion. Can J Vet Res. 2001;65:55-9 pubmed
    ..At the 0.3 mg/kg and 0.5 mg/kg dose levels, pH remained elevated for > 4 h and > 8 h, respectively. No adverse effects were observed. A significant level of 0.01 was used for all statistical methods. ..
  8. Yokoyama M, Yokoyama A, Mori S, Takahashi H, Yoshino T, Watanabe T, et al. Inducible histamine protects mice from P. acnes-primed and LPS-induced hepatitis through H2-receptor stimulation. Gastroenterology. 2004;127:892-902 pubmed
  9. Kobayashi T, Inoue I, Jenkins N, Gilbert D, Copeland N, Watanabe T. Cloning, RNA expression, and chromosomal location of a mouse histamine H2 receptor gene. Genomics. 1996;37:390-4 pubmed
    ..A weak expression was also detected in liver. An interspecific backcross analysis revealed that the mouse H2R gene, designated Hrh2, was located in the central region of chromosome 13. ..
  10. Lim H, Adami M, Guaita E, Werfel T, Smits R, De Esch I, et al. Pharmacological characterization of the new histamine H4 receptor agonist VUF 8430. Br J Pharmacol. 2009;157:34-43 pubmed publisher
    ..We compare the pharmacological profiles of a new histamine H4 receptor agonist 2-(2-guanidinoethyl)isothiourea (VUF 8430) with that of a previously described H4 receptor agonist, 4-methylhistamine...
  11. Triggiani M, Petraroli A, Loffredo S, Frattini A, Granata F, Morabito P, et al. Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor. J Allergy Clin Immunol. 2007;119:472-81 pubmed
    ..Regulation of H(1) and H(2) receptor expression in the monocyte/macrophage lineage can be relevant to the pathogenesis of allergic inflammation. ..
  12. Szabó P, Wiener Z, Tömböl Z, Kovacs A, Pocza P, Horanyi J, et al. Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors. Virchows Arch. 2009;455:133-42 pubmed publisher
    ..Adrenocortical tumorigenesis might, thus, be characterized by reduced histamine biosynthesis; furthermore, different adrenocortical tumor subtypes may show unique histamine receptor expression profiles. ..
  13. Nishibori M, Kohka Takahashi H, Mori S. [Regulation of cytokine production by histamine through H2-receptor stimulation]. Nihon Yakurigaku Zasshi. 2001;118:29-35 pubmed
    ..Histamine is a very important modulator of Th1 cytokine production in PBMC and is quite unique in triggering the cytokine cascade without inducing IL-12 production. ..
  14. Hattori Y, Sakuma I, Kanno M. Differential effects of histamine mediated by histamine H1- and H2-receptors on contractility, spontaneous rate and cyclic nucleotides in the rabbit heart. Eur J Pharmacol. 1988;153:221-9 pubmed
  15. Xie S, Schalkhausser F, Ye Q, Seifert R, Buschauer A. Effects of impromidine- and arpromidine-derived guanidines on recombinant human and guinea pig histamine H1 and H2 receptors. Arch Pharm (Weinheim). 2007;340:9-16 pubmed
    ..Our data indicate that it is difficult to obtain guanidine-type agonists with high potency and high efficacy for hH2R, but those compounds may be useful tools for exploring the antagonist binding site and constitutive activity of H1R. ..
  16. Erfanparast A, Tamaddonfard E, Farshid A, Khalilzadeh E. Effect of microinjection of histamine into the dorsal hippocampus on the orofacial formalin-induced pain in rats. Eur J Pharmacol. 2010;627:119-23 pubmed publisher
    ..These results indicate that the activation of brain neuronal histamine at the levels of the hippocampus may produce antinociception. Hippocampal histamine-induced antinociception may be mediated thorough its H(1) and H(2) receptors. ..
  17. Lippert U, Artuc M, Grützkau A, Babina M, Guhl S, Haase I, et al. Human skin mast cells express H2 and H4, but not H3 receptors. J Invest Dermatol. 2004;123:116-23 pubmed
    ..They provide new insights into the mechanisms that govern auto- and paracrine histamine-induced mast cell functions. ..
  18. Zhuang Q, Xu H, Lu X, Li B, Yung W, Wang J, et al. Histamine Excites Striatal Dopamine D1 and D2 Receptor-Expressing Neurons via Postsynaptic H1 and H2 Receptors. Mol Neurobiol. 2018;55:8059-8070 pubmed publisher
  19. Lazewska D, Kiec Kononowicz K, Elz S, Pertz H, Stark H, Schunack W. Piperidine-containing histamine H3 receptor antagonists of the carbamate series: the alkyl derivatives. Pharmazie. 2005;60:403-10 pubmed
    ..Predictions of octanol-water partition coefficient (Pallas) and metabolic fate (MetabolExpert, METEOR) were used to explore potential reasons for this absence of in vivo activity. ..
  20. Ahrens F, Gabel G, Garz B, Aschenbach J. Histamine-induced chloride secretion is mediated via H2-receptors in the pig proximal colon. Inflamm Res. 2003;52:79-85 pubmed
    ..Changes in Isc after histamine addition are primarily due to chloride secretion. The paracellular permeability is not influenced by histamine. ..
  21. Dembinski A, Warzecha Z, Ceranowicz P, Brzozowski T, Dembinski M, Konturek S, et al. Role of capsaicin-sensitive nerves and histamine H1, H2, and H3 receptors in the gastroprotective effect of histamine against stress ulcers in rats. Eur J Pharmacol. 2005;508:211-21 pubmed
    ..and that this gastroprotection is related to stimulation of histamine H1 and H3 receptors; (2) blockade of histamine H2 receptors exhibited beneficial effect on gastric mucosa against stress-induced gastric ulcers; and (3) ablation of ..
  22. Brenna E, Tielemans Y, Kleveland P, Sandvik A, Willems G, Waldum H. Effect of the histamine-2 agonist impromidine on stem cell proliferation of rat oxyntic mucosa. Scand J Gastroenterol. 1995;30:311-4 pubmed
    ..These differences were not statistically significant. The present study provides no evidence that histamine-2 receptors mediate a trophic effect on the stem cell of the rat oxyntic mucosa. ..
  23. Shankley N, Welsh N, Black J. Histamine dependence of pentagastrin-stimulated gastric acid secretion in rats. Yale J Biol Med. 1992;65:613-9 pubmed
    ..Potentiation was observed, however, between other combinations of stimuli, for example, between vagal nerve and pentagastrin stimulation. The physiological consequences of these results are discussed. ..
  24. Zawilska J, Woldan Tambor A, Nowak J. Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]tiotidine binding. J Neurochem. 2002;81:935-46 pubmed
    ..It is suggested that the studied receptors represent either an avian-specific H(2) -like HA receptors or a novel subtype of HA receptors. ..
  25. Eidi M, Oryan S, Eidi A, Sepehrara L. Effect of morphine, naloxone and histamine system on water intake in adult male rats. Eur J Pharmacol. 2003;478:105-10 pubmed
    ..It is concluded that the histaminergic system may have a close interaction with morphine and naloxone on drinking behavior. ..
  26. Tsuru H, Kohno S, Iwata M, Shigei T. Characterization of histamine receptors in isolated rabbit veins. J Pharmacol Exp Ther. 1987;243:696-702 pubmed
  27. Burde R, Buschauer A, Seifert R. Characterization of histamine H2-receptors in human neutrophils with a series of guanidine analogues of impromidine. Are cell type-specific H2-receptors involved in the regulation of NADPH oxidase?. Naunyn Schmiedebergs Arch Pharmacol. 1990;341:455-61 pubmed
    ..In the latter system, guanidines are full H2-agonists with potencies of up to 125-fold of that of histamine. Our data indicate that guanidines inhibit O2- formation in human neutrophils via H2-receptors.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  28. Motoki A, Adachi N, Liu K, Takahashi H, Nishibori M, Yorozuya T, et al. Suppression of ischaemia-induced cytokine release by dimaprit and amelioration of liver injury in rats. Basic Clin Pharmacol Toxicol. 2008;102:394-8 pubmed publisher
    ..Since interleukin-12 facilitates cell-mediated cytotoxicity, the protective effect of dimaprit may be attributed to regulation of cytokine release during reperfusion. ..
  29. Suh H, Chung K, Kim Y, Huh S, Song D. Effects of histamine receptor antagonists injected intrathecally on antinociception induced by opioids administered intracerebroventricularly in the mouse. Neuropeptides. 1999;33:121-9 pubmed
    ..Spinal H2 receptors appear to be involved in supraspinally administered morphine, b-endorphin- and U50,488H-induced antinociception but not DPDPE-induced antinociception. ..
  30. Yoshida M, Takahashi Y, Inoue S. Histamine induces melanogenesis and morphologic changes by protein kinase A activation via H2 receptors in human normal melanocytes. J Invest Dermatol. 2000;114:334-42 pubmed
    ..Taken together, we show here that histamine induces melanogenesis of human cultured melanocytes by protein kinase A activation via H2 receptors. ..
  31. Holden C, Chan S, Norris S, Hanifin J. Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes. Agents Actions. 1987;22:36-42 pubmed
    ..e. increased catabolism and a net reduction in cAMP levels. The localization of this effect predominantly to monocytes indicates a potentially important mechanism for histamine action on immune regulation. ..
  32. Murata Y, Tanimoto A, Wang K, Tsutsui M, Sasaguri Y, De Corte F, et al. Granulocyte macrophage-colony stimulating factor increases the expression of histamine and histamine receptors in monocytes/macrophages in relation to arteriosclerosis. Arterioscler Thromb Vasc Biol. 2005;25:430-5 pubmed
    ..In monocytic U937 cells, GM-CSF upregulated the expression of histamine and HH1R. Coordinated expression of histamine and its receptors by GM-CSF would participate in atherogenesis by affecting monocytic and SMC gene expression. ..
  33. Boertje S, Ward S, Robinson A. H2-receptors mediate histamine-induced variations in the permeability of the blood-brain barrier of rats. Res Commun Chem Pathol Pharmacol. 1992;76:143-54 pubmed
    ..The alterations in the permeability of the BBB did not correlate with variations in blood pressure produced by histamine. ..
  34. Eriks J, Sterk G, van der Aar E, Van Acker S, van der Goot H, Timmerman H. 4- or 5- (omega-aminoalkyl) thiazoles and derivatives; new selective H2-receptor agonists. Agents Actions Suppl. 1991;33:301-14 pubmed
    ..In a series of impromidine analogues the 3- [4(5)-imidazolyl]propyl moiety was replaced by the more H2-receptor specific 3-(4- or 5-thiazolyl)propyl fragment resulting in potent and selective full H2-receptor agonists. ..
  35. Onaran H, Bökesoy T. Heterogeneity of histamine H2-receptor mediated responses in the rabbit aorta. Agents Actions. 1988;24:250-4 pubmed
    ..A nonspecific smooth muscle relaxant, papaverine had homogeneous activity along the vessel, suggesting receptor specific nature of the observed heterogeneity. ..
  36. Knigge U, Willems E, Kjaer A, Jørgensen H, Warberg J. Histaminergic and catecholaminergic interactions in the central regulation of vasopressin and oxytocin secretion. Endocrinology. 1999;140:3713-9 pubmed
    ..The present findings further substantiate the role of histaminergic neurons in the central regulation of neurohypophysial hormone secretion...
  37. Kenakin T. What systems can and can't do. Br J Pharmacol. 2008;153:841-3 pubmed publisher
  38. Suh B, Lee H, Jun D, Chun J, Lee J, Kim K. Inhibition of H2 histamine receptor-mediated cation channel opening by protein kinase C in human promyelocytic cells. J Immunol. 2001;167:1663-71 pubmed
    ..Both effects of histamine were selectively inhibited probably by the delta isoform of PKC in HL-60 cells. ..
  39. Aikou S, Fukushima Y, Ogawa M, Nozaki K, Saito T, Matsui T, et al. Alterations in gastric mucosal lineages before or after acute oxyntic atrophy in gastrin receptor and H2 histamine receptor-deficient mice. Dig Dis Sci. 2009;54:1625-35 pubmed publisher
    ..The H(2) receptor and gastrin receptor do not affect emergence of SPEM. However, it is suggested that the absence of H(2) receptor signaling causes a delay in the maturation of chief cells from mucous neck cells. ..
  40. Okabe S. [Acetic acid-induced gastro-duodenal ulcers in experimental animals--examples of serendipity and pseudoserendipity]. Yakugaku Zasshi. 2005;125:17-29 pubmed
    ..Gastrin-transgenic mice infected with H. pylori revealed to develop gastric cancer. The hypothesis for the origin of parietal cells was provided. ..
  41. Ikawa Y, Yonekawa T, Ohkuni Y, Kuribayashi M, Fukino K, Ueno K. A comparative study of histamine activities on differentiation of osteoblasts and osteoclasts. J Toxicol Sci. 2007;32:555-64 pubmed
    ..This observation is consistent with the traditionally recognized histamine action of bone resorption at the osteoclast site. ..
  42. Repka Ramirez M. New concepts of histamine receptors and actions. Curr Allergy Asthma Rep. 2003;3:227-31 pubmed
    ..There is great excitement due to preliminary findings that H3 receptors act as neural inhibitory autoreceptors, and H4 receptors might modulate immune cell functions. ..
  43. Sarker M, Fraser P. The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat. J Physiol. 2002;540:209-18 pubmed
    ..In conclusion, the histamine H(2) receptor appears to signal via cGMP that is generated by a NO and soluble guanylyl cyclase, while bradykinin B(2) receptor also signals via cGMP but through particulate guanylyl cyclase. ..
  44. Cooke H, Wang Y, Wray D, O DORISIO M, Woltering E, Coy D, et al. A multi-tyrosinated sst1/2 receptor preferring somatostatin agonist inhibits reflex and immune-mediated secretion in the guinea pig colon. Regul Pept. 2003;114:51-60 pubmed
    ..The results suggest that WOC 3B, a somatostatin analogue containing three tyrosine residues, has anti-secretory effects due to activation of somatostatin sst1 and sst2 receptors on enteric neurons. ..
  45. Ferreira P, de Oliveira C, de Oliveira A, Lopes M, Alzamora F, Vieira M. A lyophilized aqueous extract of Maytenus ilicifolia leaves inhibits histamine-mediated acid secretion in isolated frog gastric mucosa. Planta. 2004;219:319-24 pubmed
    ..such as inhibition of histamine biosynthesis and/or histamine release can not be ruled out, our data suggest that LAEMIL, like cimetidine, reduces acid secretion in the isolated frog gastric mucosa by antagonising histamine H2 receptors.
  46. Rozenberg I, Sluka S, Rohrer L, Hofmann J, Becher B, Akhmedov A, et al. Histamine H1 receptor promotes atherosclerotic lesion formation by increasing vascular permeability for low-density lipoproteins. Arterioscler Thromb Vasc Biol. 2010;30:923-30 pubmed publisher
    ..These data open novel perspectives for the prevention and treatment of atherosclerotic vascular disease. ..
  47. Mobarakeh J, Takahashi K, Sakurada S, Nishino S, Watanabe H, Kato M, et al. Enhanced antinociception by intracerebroventricularly administered orexin A in histamine H1 or H2 receptor gene knockout mice. Pain. 2005;118:254-62 pubmed
    ..Thus, the blocking of the histamine H1 or H2 receptor may produce antinociception and enhance the orexin A-induced antinociception. ..
  48. Horvath Z, Pallinger E, Horváth G, Jelinek I, Falus A, Buzas E. Histamine H1 and H2 receptors but not H4 receptors are upregulated during bone marrow regeneration. Cell Immunol. 2006;244:110-5 pubmed
  49. Fukushima Y, Otsuka H, Ishikawa M, Asano T, Anai M, Katsube T, et al. Potent and long-lasting action of lafutidine on the human histamine H(2) receptor. Digestion. 2001;64:155-60 pubmed
    ..78 x 10(-7) M lafutidine, but not with 10(-5) M famotidine, had marked inhibitory effects which persisted as long as after extensive washing. Lafutidine shows a potent and long-lasting antagonism on the human H(2)R. ..
  50. Nagahama K, Yamato M, Kato S, Takeuchi K. Protective effect of lafutidine, a novel H2-receptor antagonist, on reflux esophagitis in rats through capsaicin-sensitive afferent neurons. J Pharmacol Sci. 2003;93:55-61 pubmed
    ..The latter mechanism, not shared by cimetidine, may be due to the interaction of lafutidine with unidentified sites on sensory neurons other than VR1. ..
  51. Cianchi F, Cortesini C, Schiavone N, Perna F, Magnelli L, Fanti E, et al. The role of cyclooxygenase-2 in mediating the effects of histamine on cell proliferation and vascular endothelial growth factor production in colorectal cancer. Clin Cancer Res. 2005;11:6807-15 pubmed
    ..These effects are likely to be mediated by increasing COX-2-related PGE2 production in COX-2-expressing colon cancer cells. ..
  52. Dux M, Schwenger N, Messlinger K. Possible role of histamine (H1- and H2-) receptors in the regulation of meningeal blood flow. Br J Pharmacol. 2002;137:874-80 pubmed
    ..In addition, H(1)-receptors on smooth muscle cells may mediate vasoconstriction. ..
  53. Koizumi H, Ohkawara A. H2 histamine receptor-mediated increase in intracellular Ca2+ in cultured human keratinocytes. J Dermatol Sci. 1999;21:127-32 pubmed
    ..Epinephrine response was not affected by these antihistamines. Thus, it is considered that H2 antihistamines specifically block histamine-mediated increase in intracellular Ca2+ of cultured normal human keratinocytes. ..