Gene Symbol: Hrh3
Description: histamine receptor H3
Alias: AW049250, H3R, HH3R, histamine H3 receptor
Species: mouse
Products:     Hrh3

Top Publications

  1. Butterfield R, Sudweeks J, Blankenhorn E, Korngold R, Marini J, Todd J, et al. New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice. J Immunol. 1998;161:1860-7 pubmed
    ..Importantly, eae5 and eae7 are syntenic with human chromosomes 6p21 and 17q22, respectively, two regions of potential significance recently identified in human multiple sclerosis genome scans. ..
  2. Toyota H, Dugovic C, Koehl M, Laposky A, Weber C, Ngo K, et al. Behavioral characterization of mice lacking histamine H(3) receptors. Mol Pharmacol. 2002;62:389-97 pubmed
    ..These data indicate that the H(3) receptor-deficient mouse represents a valuable model for studying histaminergic regulation of a variety of behaviors and neurotransmitter systems, including dopamine and acetylcholine. ..
  3. Takahashi K, Suwa H, Ishikawa T, Kotani H. Targeted disruption of H3 receptors results in changes in brain histamine tone leading to an obese phenotype. J Clin Invest. 2002;110:1791-9 pubmed
    ..These results suggest that neuronal histamine is a mediator of body-weight homeostasis and that neuronal histamine functions through H3 receptors in mice. ..
  4. Hofstra C, Desai P, Thurmond R, Fung Leung W. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther. 2003;305:1212-21 pubmed
    ..In summary, histamine was shown to mediate signaling and chemotaxis of mast cells via the H4 receptor. This mechanism might be responsible for mast cell accumulation in allergic tissues. ..
  5. Chen J, Liu C, Lovenberg T. Molecular and pharmacological characterization of the mouse histamine H3 receptor. Eur J Pharmacol. 2003;467:57-65 pubmed
    ..Taken together, these findings allow a further appreciation of the histamine H(3) receptor at the molecular level and provide an additional species to assist in the pharmacological assessment of histamine H(3) receptor function. ..
  6. Beghdadi W, Porcherie A, Schneider B, Morisset S, Dubayle D, Peronet R, et al. Histamine H(3) receptor-mediated signaling protects mice from cerebral malaria. PLoS ONE. 2009;4:e6004 pubmed publisher
    ..In the present work, we explored the role of histamine signaling via the histamine H3 receptor (H3R) in the pathogenesis of murine CM...
  7. Teuscher C, Subramanian M, Noubade R, Gao J, Offner H, Zachary J, et al. Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. Proc Natl Acad Sci U S A. 2007;104:10146-51 pubmed
    ..Our data suggest that pharmacological targeting of the H3R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby ..
  8. Panula P, Nuutinen S. Histamine and H3 receptor in alcohol-related behaviors. J Pharmacol Exp Ther. 2011;336:9-16 pubmed publisher
    ..H(3)R ligands may have significant effects on alcohol addiction. ..
  9. Nuutinen S, Lintunen M, Vanhanen J, Ojala T, Rozov S, Panula P. Evidence for the role of histamine H3 receptor in alcohol consumption and alcohol reward in mice. Neuropsychopharmacology. 2011;36:2030-40 pubmed publisher
    Recent research suggests that histamine H3 receptor (H3R) antagonism may diminish motivational aspects of alcohol dependence. We studied the role of H3Rs in alcohol-related behaviors using H3R knockout (KO) mice and ligands...

More Information


  1. Yoshimoto R, Miyamoto Y, Takahashi K, Kotani H, Kanatani A, Tokita S. Impaired drinking response in histamine H3 receptor knockout mice following dehydration or angiotensin-II challenge. Pharmacol Biochem Behav. 2006;84:504-10 pubmed
    ..In water-replete rats, intracerebroventricular (i.c.v.) administration of R-alpha-methylhistamine (RalphaMeHA), an H3R agonist, elicited drinking behavior. In contrast, i.c.v...
  2. Krementsov D, Wall E, Martin R, Subramanian M, Noubade R, del Rio R, et al. Histamine H(3) receptor integrates peripheral inflammatory signals in the neurogenic control of immune responses and autoimmune disease susceptibility. PLoS ONE. 2013;8:e62743 pubmed publisher
    Histamine H(3) receptor (Hrh3/H(3)R) is primarily expressed by neurons in the central nervous system (CNS) where it functions as a presynaptic inhibitory autoreceptor and heteroreceptor...
  3. Chepkova A, Yanovsky E, Parmentier R, Ohtsu H, Haas H, Lin J, et al. Histamine receptor expression, hippocampal plasticity and ammonia in histidine decarboxylase knockout mice. Cell Mol Neurobiol. 2012;32:17-25 pubmed publisher
    ..We conclude that the absence of neuronal histamine results in subtle changes in hippocampal synaptic transmission and plasticity associated with alteration in the expression of H3 receptors...
  4. Encinas J, Lees M, Sobel R, Symonowicz C, Greer J, Shovlin C, et al. Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis in a cross between SJL/J and B10.S mice. J Immunol. 1996;157:2186-92 pubmed
    ..In addition, several other regions showing some evidence of linkage (p < or = 0.05) with clinical disease were found. ..
  5. Chen Y, Paavola J, Stegajev V, Stark H, Chazot P, Wen J, et al. Activation of histamine H3 receptor decreased cytoplasmic Ca(2+) imaging during electrical stimulation in the skeletal myotubes. Eur J Pharmacol. 2015;754:173-8 pubmed publisher
    Histamine is a neurotransmitter and chemical mediator in multiple physiological processes. Histamine H3 receptor is expressed in the nervous system, heart, and gastrointestinal tract; however, little is known about H3 receptor in ..
  6. Parmentier R, Anaclet C, Guhennec C, Brousseau E, Bricout D, Giboulot T, et al. The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders. Biochem Pharmacol. 2007;73:1157-71 pubmed
  7. Rizk A, Curley J, Robertson J, Raber J. Anxiety and cognition in histamine H3 receptor-/- mice. Eur J Neurosci. 2004;19:1992-6 pubmed
    ..Acute H3R stimulation or blockade with selective agonists and antagonists suggests a role for H3R in anxiety and cognition...
  8. Saligrama N, Case L, del Rio R, Noubade R, Teuscher C. Systemic lack of canonical histamine receptor signaling results in increased resistance to autoimmune encephalomyelitis. J Immunol. 2013;191:614-22 pubmed publisher
    ..Using HR-deficient mice, our laboratory has demonstrated that H1R, H2R, H3R, and H4R play important roles in EAE pathogenesis, by regulating encephalitogenic T cell responses, cytokine ..
  9. Rozov S, Porkka Heiskanen T, Panula P. On the Role of Histamine Receptors in the Regulation of Circadian Rhythms. PLoS ONE. 2015;10:e0144694 pubmed publisher
    ..The aim of this study was to examine whether histamine mediates its effects on the circadian system through Hrh1 or Hrh3 receptors. We assessed both diurnal and free-running locomotor activity rhythms of Hrh1-/- and Hrh3-/- mice...
  10. Henry M, Zheng S, Duan C, Patel B, Vassileva G, Sondey C, et al. Antidiabetic properties of the histamine H3 receptor protean agonist proxyfan. Endocrinology. 2011;152:828-35 pubmed publisher
    Proxyfan is a histamine H3 receptor protean agonist that can produce a spectrum of pharmacological effects including agonist, inverse agonist, and antagonist...
  11. Rapanelli M, Frick L, Pogorelov V, Ohtsu H, Bito H, Pittenger C. Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders. Transl Psychiatry. 2017;7:e1013 pubmed publisher
    ..We found elevated expression of the histamine H3 receptor in the striatum of Hdc knockout mice...
  12. Gondard E, Anaclet C, Akaoka H, Guo R, Zhang M, Buda C, et al. Enhanced histaminergic neurotransmission and sleep-wake alterations, a study in histamine H3-receptor knock-out mice. Neuropsychopharmacology. 2013;38:1015-31 pubmed publisher
    ..of the histaminergic system, we compared the cortical EEG and sleep-wake states of H3-receptor knockout (H3R-/-) and wild-type mouse littermates. We found that H3R-/-mice had rich phenotypes...
  13. Koyama M, Seyedi N, Fung Leung W, Lovenberg T, Levi R. Norepinephrine release from the ischemic heart is greatly enhanced in mice lacking histamine H3 receptors. Mol Pharmacol. 2003;63:378-82 pubmed
    ..Inasmuch as excessive NE release is clinically recognized as a major cause of arrhythmic cardiac dysfunction, our findings reveal a significant cardioprotective role of H(3)R on cSNE. ..
  14. Koyama M, Heerdt P, Levi R. Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors. Biochem Biophys Res Commun. 2003;306:792-6 pubmed
    ..Since malignant tachyarrhythmias cause sudden death in ischemic heart disease, attenuation of NE release by selective H(3)R agonists may represent a new approach in the prevention and treatment of ischemic arrhythmias. ..
  15. Nakamura T, Yoshikawa T, Noguchi N, Sugawara A, Kasajima A, Sasano H, et al. The expression and function of histamine H? receptors in pancreatic beta cells. Br J Pharmacol. 2014;171:171-85 pubmed publisher
    ..Histamine H? receptors were expressed in mouse beta cells and could play a role in insulin secretion and, possibly, beta cell proliferation. ..
  16. Yokota E, Kuyama S, Sugimoto Y, Ogawa M, Kamei C. Participation of histamine H3 receptors in experimental allergic rhinitis of mice. J Pharmacol Sci. 2008;108:206-11 pubmed
    ..These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy. ..
  17. Okuda T, Zhang D, Shao H, Okamura N, Takino N, Iwamura T, et al. Methamphetamine- and 3,4-methylenedioxymethamphetamine-induced behavioral changes in histamine H3-receptor knockout mice. J Pharmacol Sci. 2009;111:167-74 pubmed
    ..These findings suggest that deficiency in histamine H(3) receptors may have inhibitory effects on psychostimulant-induced increase in locomotion, but insignificant effects on the reward. ..
  18. Saligrama N, Noubade R, Case L, del Rio R, Teuscher C. Combinatorial roles for histamine H1-H2 and H3-H4 receptors in autoimmune inflammatory disease of the central nervous system. Eur J Immunol. 2012;42:1536-46 pubmed publisher
    ..These findings support the concept that combined pharmacological targeting of HRs may be an appropriate ancillary DMT in MS and other immunopathologic diseases. ..
  19. Mobarakeh J, Takahashi K, Yanai K. Enhanced morphine-induced antinociception in histamine H3 receptor gene knockout mice. Neuropharmacology. 2009;57:409-14 pubmed publisher
    Previous studies have implicated a potential role for histamine H3 receptor in pain processing...
  20. Tritto S, Botta L, Zampini V, Zucca G, Valli P, Masetto S. Calyx and dimorphic neurons of mouse Scarpa's ganglion express histamine H3 receptors. BMC Neurosci. 2009;10:70 pubmed publisher
    ..Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve...
  21. Ding W, Lin L, Xiao Z, Zou H, Duan Z, Dai J. Multiple sequence elements determine the intron retention in histamine H3 receptors in rats and mice. Int J Biochem Cell Biol. 2009;41:2281-6 pubmed publisher
    ..The results provide insight into special alternative splicing regulation in H(3) receptors. ..
  22. Zhou F, Xu J, Zhao Y, Ledoux M, Zhou F. Opposite functions of histamine H1 and H2 receptors and H3 receptor in substantia nigra pars reticulata. J Neurophysiol. 2006;96:1581-91 pubmed
    ..In Parkinson's disease, histamine innervation and histamine H3 receptor expression in SNr may be increased...
  23. Rapanelli M, Frick L, Horn K, Schwarcz R, Pogorelov V, Nairn A, et al. The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons. J Biol Chem. 2016;291:21042-21052 pubmed
    ..Receptors for histamine, especially the H3 receptor (H3R), are highly expressed in the striatum, the primary input nucleus of the basal ganglia, but their effects on this ..
  24. Shi Y, Sheng R, Zhong T, Xu Y, Chen X, Yang D, et al. Identification and characterization of ZEL-H16 as a novel agonist of the histamine H3 receptor. PLoS ONE. 2012;7:e42185 pubmed publisher
    The histamine H3 receptor (H3R) has been recognized as a promising target for the treatment of various central and peripheral nervous system diseases...
  25. Mariottini C, Scartabelli T, Bongers G, Arrigucci S, Nosi D, Leurs R, et al. Activation of the histaminergic H3 receptor induces phosphorylation of the Akt/GSK-3 beta pathway in cultured cortical neurons and protects against neurotoxic insults. J Neurochem. 2009;110:1469-78 pubmed publisher
    ..Hence, we uncovered a yet unexplored action of the H(3)R that may help understand the impact of H(3)R signaling in the CNS. ..
  26. Yoshimoto R, Kanatani A, Tokita S. Distinctive role of central histamine H3 receptor in various orexigenic pathways. Eur J Pharmacol. 2008;579:229-32 pubmed
    ..These results indicate distinctive roles of histamine H(3) receptors in various orexigenic pathways. ..
  27. Moreno E, Hoffmann H, Gonzalez SepĂșlveda M, Navarro G, Casado V, CortĂ©s A, et al. Dopamine D1-histamine H3 receptor heteromers provide a selective link to MAPK signaling in GABAergic neurons of the direct striatal pathway. J Biol Chem. 2011;286:5846-54 pubmed publisher
    ..These results indicate that D(1)-H(3) receptor heteromers work as processors integrating dopamine- and histamine-related signals involved in controlling the function of striatal neurons of the direct striatal pathway. ..
  28. Kononoff Vanhanen J, Nuutinen S, Tuominen M, Panula P. Histamine H3 Receptor Regulates Sensorimotor Gating and Dopaminergic Signaling in the Striatum. J Pharmacol Exp Ther. 2016;357:264-72 pubmed publisher
    ..Histamine also regulates alcohol reward and consumption via H3 receptor (H3R), possibly through an interaction with the brain dopaminergic system...