Advertisement

Histamine H1 Receptor Gene Expression and Drug Action of Antihistamines

  • Hiroyuki FukuiEmail author
  • Hiroyuki Mizuguchi
  • Hisao Nemoto
  • Yoshiaki Kitamura
  • Yoshiki Kashiwada
  • Noriaki Takeda
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 241)

Abstract

The upregulation mechanism of histamine H1 receptor through the activation of protein kinase C-δ (PKCδ) and the receptor gene expression was discovered. Levels of histamine H1 receptor mRNA and IL-4 mRNA in nasal mucosa were elevated by the provocation of nasal hypersensitivity model rats. Pretreatment with antihistamines suppressed the elevation of mRNA levels. Scores of nasal symptoms were correlatively alleviated to the suppression level of mRNAs above. A correlation between scores of nasal symptoms and levels of histamine H1 receptor mRNA in the nasal mucosa was observed in patients with pollinosis. Both scores of nasal symptoms and the level of histamine H1 receptor mRNA were improved by prophylactic treatment of antihistamines. Similar to the antihistamines, pretreatment with antiallergic natural medicines showed alleviation of nasal symptoms with correlative suppression of gene expression in nasal hypersensitivity model rats through the suppression of PKCδ. Similar effects of antihistamines and antiallergic natural medicines support that histamine H1 receptor-mediated activation of histamine H1 receptor gene expression is an important signaling pathway for the symptoms of allergic diseases. Antihistamines with inverse agonist activity showed the suppression of constitutive histamine H1 receptor gene expression, suggesting the advantage of therapeutic effect.

Keywords

Allergic disease-sensitive gene Histamine H1 receptor Natural medicine Pollinosis Protein kinase C 

Abbreviations

GPCR

G-protein-coupled receptor

HDC

Histidine decarboxylase

H1R

Histamine H1 receptor

IL-5

Interleukin-5

PARP-1

Poly(ADP-ribose) polymerase-1

PKC

Protein kinase C

PMA

Phorbol-12-myristate-13-acetate

TDI

Toluene 2,4-diisocyanate

References

  1. Bakker RA, Schoonus SB, Smit MJ, Timmerman H, Leurs R (2002) Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling. Mol Pharmacol 60(5):1133–1142Google Scholar
  2. Das AK, Yoshimura S, Mishima R, Fujimoto K, Mizuguchi H, Dev S, Wakayama Y, Kitamura Y, Horio S, Takeda N, Fukui H (2007) Stimulation of histamine H1 receptor up-regulates histamine H1 receptor itself through activation of receptor gene transcription. J Pharmacol Sci 103(4):374–382CrossRefPubMedGoogle Scholar
  3. Das AK, Mizuguchi H, Kodama M, Dev S, Umehara H, Kitamura Y, Matsushita C, Takeda N, Fukui H (2009) Sho-seiryu-to suppresses histamine signaling at the transcriptional level in TDI-sensitized nasal allergy model rats. Allergol Int 58(1):81–88. doi: 10.2332/allergolint CrossRefPubMedGoogle Scholar
  4. Dev S, Mizuguchi H, Das AK, Maeyama K, Horinaga S, Kato S, Tamada M, Hattori M, Umehara H, Fukui H (2009) Kujin suppresses histamine signaling at the transcriptional level in toluene 2,4-diisocyanate-sensitized rats. J Pharmacol Sci 109(4):606–617CrossRefPubMedGoogle Scholar
  5. Dinh QT, Cryer A, Dinh S, Peiser C, Wu S, Springer J, Hamelmann E, Klapp BF, Heppt W, Fischer A (2005) Transcriptional up-regulation of histamine receptor-1 in epithelial, mucus and inflammatory cells in perennial allergic rhinitis. Clin Exp Allergy 35(11):1443–1448CrossRefPubMedGoogle Scholar
  6. Hattori M, Mizuguchi H, Baba Y, Ono S, Nakano T, Zhang Q, Sasaki Y, Kobayashi M, Kitamura Y, Takeda N, Fukui H (2013) Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-δ/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells. Int Immunopharmacol 15(2):232–239. doi: 10.1016/j.intimp CrossRefPubMedGoogle Scholar
  7. Hishinuma S, Komazaki H, Fukui H, Shoji M (2010) Ubiquitin/proteasome-dependent down-regulation following clathrin-mediated internalization of histamine H1-receptors in Chinese hamster ovary cells. J Neurochem 113(4):990–1001CrossRefPubMedGoogle Scholar
  8. Horio S, Kato T, Ogawa M, Fujimoto K, Fukui H (2004) Two threonine residues and two serine residues in the second and third intracellular loops are both involved in histamine H1 receptor downregulation. FEBS Lett 573(1–3):226–230CrossRefPubMedGoogle Scholar
  9. Iriyoshi N, Takeuchi K, Yuta A, Ukai K, Sakakura Y (1996) Increased expression of histamine H1 receptor mRNA in allergic rhinitis. Clin Exp Allergy 26(4):379–385CrossRefPubMedGoogle Scholar
  10. Kitamura Y, Miyoshi A, Murata Y, Kalubi B, Fukui H, Takeda N (2004) Effect of glucocorticoid on upregulation of histamine H1 receptor mRNA in nasal mucosa of rats sensitized by exposure to toluene diisocyanate. Acta Otolaryngol 124(9):1053–1058CrossRefPubMedGoogle Scholar
  11. Kitamura Y, Nakagawa H, Fujii T, Sakoda T, Enomoto T, Mizuguchi H, Fukui H, Takeda N (2015) Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit. J Pharmacol Sci 129(3):183–187. doi: 10.1016/j.jphs CrossRefPubMedGoogle Scholar
  12. Leurs R, Church MK, Taglialatela M (2002) H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin Exp Allergy 32(4):489–498Google Scholar
  13. Mizuguchi H, Hatano M, Matsushita C, Umehara H, Kuroda W, Kitamura Y, Takeda N, Fukui H (2008) Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats. J Pharmacol Sci 108(4):480–486. Erratum in: J Pharmacol Sci 109(2):324, 2009Google Scholar
  14. Mizuguchi H, Kitamura Y, Kondo Y, Kuroda W, Yoshida H, Miyamoto Y, Hattori M, Fukui H, Takeda N (2010) Preseasonal prophylactic treatment with antihistamines suppresses nasal symptoms and expression of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis. Methods Find Exp Clin Pharmacol 32(10):745–748. doi:10.1358/mfGoogle Scholar
  15. Mizuguchi H, Terao T, Kitai M, Ikeda M, Yoshimura Y, Das AK, Kitamura Y, Takeda N, Fukui H (2011a) Involvement of protein kinase Cdelta/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expression in HeLa cells. J Biol Chem 286(35):30542–30551. doi: 10.1074/jbc.M111.253104 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Mizuguchi H, Ono S, Hattori M, Fukui H (2011b) Inverse agonistic activity of antihistamines and suppression of histamine H1 receptor gene expression. J Pharmacol Sci 118(1):117–121CrossRefPubMedGoogle Scholar
  17. Mizuguchi H, Miyagi K, Terao T, Sakamoto N, Yamawaki Y, Adachi T, Ono S, Sasaki Y, Yoshimura Y, Kitamura Y, Takeda N, Fukui H (2012) PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H(1) receptor. Sci Rep 2(916):1–11. doi: 10.1038/srep00916
  18. Mizuguchi H, Ono S, Hattori M, Sasaki Y, Fukui H (2013) Usefulness of HeLa cells to evaluate inverse agonistic activity of antihistamines. Int Immunopharmacol 15(3):539–543. doi: 10.1016/j.intimp.2013.02.009 CrossRefPubMedGoogle Scholar
  19. Mizuguchi H, Nariai Y, Kato S, Nakano T, Kanayama T, Kashiwada Y, Nemoto H, Kawazoe K, Takaishi Y, Kitamura Y, Takeda N, Fukui H (2015) Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes. Pharmacol Res Perspect 3(5):e00166. doi: 10.1002/prp2 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Nariai Y, Mizuguchi H, Ogasawara T, Nagai H, Sasaki Y, Okamoto Y, Yoshimura Y, Kitamura Y, Nemoto H, Takeda N, Fukui H (2015) Disruption of heat shock protein 90 (Hsp90)-protein kinase Cδ (PKCδ) interaction by (-)-maackiain suppresses histamine H1 receptor gene transcription in HeLa cells. J Biol Chem 290(45):27393–27402. doi: 10.1074/jbc.M115.657023 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Ohuchi Y, Yanai K, Sakurai E, Fukui H, Yanagisawa T, Watanabe T (1998) Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors: a relationship between its sensitivity and the density of H1 receptors. Int J Mol Med 1(2):355–360PubMedGoogle Scholar
  22. Shill MC, Mizuguchi H, Karmakar S, Kadota T, Mukherjee PK, Kitamura Y, Kashiwada Y, Nemoto H, Takeda N, Fukui H (2015) A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C-δ-dependent signaling pathway. Int Immunopharmacol 30:18–26. doi: 10.1016/j.intimp CrossRefPubMedGoogle Scholar
  23. Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S (2011) Structure of the human histamine H1 receptor complex with doxepin. Nature 475(7354):65–70. doi: 10.1038/nature10236 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Wu RL, Anthes JC, Kreutner W, Harris AG, West RE Jr (2004) Desloratadine inhibits constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 receptor. Int Arch Allergy Immunol 135(4):313–318CrossRefPubMedGoogle Scholar
  25. Yamashita M, Fukui H, Sugama K, Horio Y, Ito S, Mizuguchi H, Wada H (1991) Expression cloning of a cDNA encoding the bovine histamine H1 receptor. Proc Natl Acad Sci U S A 88(24):11515–11519CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© SpringerInternationalPublishingSwitzerland 2016

Authors and Affiliations

  • Hiroyuki Fukui
    • 1
    Email author
  • Hiroyuki Mizuguchi
    • 2
  • Hisao Nemoto
    • 3
  • Yoshiaki Kitamura
    • 4
  • Yoshiki Kashiwada
    • 5
  • Noriaki Takeda
    • 4
  1. 1.Department of Molecular Studies for Incurable Diseases, Institute of Biomedical Sciences, Fujii Memorial Institute of Medical ScienceTokushima University Graduate SchoolTokushimaJapan
  2. 2.Department of Molecular Pharmacology, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
  3. 3.Department of Pharmaceutical Chemistry, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
  4. 4.Department of Otolaryngology and Communicative Neuroscience, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
  5. 5.Department of Pharmacognosy, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan

Personalised recommendations