Advertisement

Histamine H2 Receptor Biased Signaling Methods

  • Natalia C. FernándezEmail author
  • Carina Shayo
  • Carlos Davio
  • Federico Monczor
Protocol
Part of the Methods in Pharmacology and Toxicology book series (MIPT)

Abstract

Advances in the study of G protein-coupled receptors (GPCRs) allow understanding of the existence of multiple possible receptor conformational states. Among the wide range of possible events that could be mediated by a receptor (second messenger modulation, dimerization, desensitization, internalization, G protein-dependent signaling, gene regulation, etc), the ligand–receptor complex governs the ultimate downstream signaling event and the final cellular response. To analyze the pluridimensional aspect of ligand efficacy, there is a need to employ a wide range of experimental tools that enable the study of receptor behaviors.

In an attempt to contribute to the study and comprehension of the biased behavior of histamine H2 receptor (H2R) ligands, the aim of this chapter is to provide experimental tools that facilitate the exploration and analysis of the pluridimensional nature of H2R ligands. We hope that in the future it would be possible to develop ligands that take advantage of biased signaling by selectively activating the beneficial signaling events of the H2R and blocking the undesired ones.

Key words

Biased agonism Biased quantification Functional selectivity Pluridimensional efficacy Receptor conformation 

References

  1. 1.
    Langley JN (1905) On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curari. J Physiol 33:374–413PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Prull CR (2003) Part of a scientific master plan? Paul Ehrlich and the origins of his receptor concept. Med Hist 47:332–356PubMedPubMedCentralGoogle Scholar
  3. 3.
    Hill A (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 40:4–7Google Scholar
  4. 4.
    Black JW, Leff P (1983) Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci 220:141–162PubMedCrossRefGoogle Scholar
  5. 5.
    Johnston CA, Siderovski DP (2007) Receptor-mediated activation of heterotrimeric G-proteins: current structural insights. Mol Pharmacol 72:219–230PubMedCrossRefGoogle Scholar
  6. 6.
    Wettschureck N, Offermanns S (2005) Mammalian G proteins and their cell type specific functions. Physiol Rev 85:1159–1204PubMedCrossRefGoogle Scholar
  7. 7.
    Luttrell LM, van Biesen T, Hawes BE et al (1997) G-protein-coupled receptors and their regulation: activation of the MAP kinase signaling pathway by G-protein-coupled receptors. Adv Second Messenger Phosphoprotein Res 31:263–277PubMedCrossRefGoogle Scholar
  8. 8.
    Lefkowitz RJ, Shenoy SK (2005) Transduction of receptor signals by beta-arrestins. Science 308:512–517PubMedCrossRefGoogle Scholar
  9. 9.
    Stephenson RP (1997) A modification of receptor theory. 1956. Br J Pharmacol 120:106–120PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Perez DM, Karnik SS (2005) Multiple signaling states of G-protein-coupled receptors. Pharmacol Rev 57:147–161PubMedCrossRefGoogle Scholar
  11. 11.
    Kenakin T (2009) Pharmacology primer: theory, applications and methods, 3rd edn. Elsevier Inc United KindomGoogle Scholar
  12. 12.
    Neubig RR, Spedding M, Kenakin T et al (2003) International union of pharmacology committee on receptor nomenclature and drug classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev 55:597–606PubMedCrossRefGoogle Scholar
  13. 13.
    Strange PG (2002) Mechanisms of inverse agonism at G-protein-coupled receptors. Trends Pharmacol Sci 23:89–95PubMedCrossRefGoogle Scholar
  14. 14.
    Ligeti E, Csepanyi-Komi R, Hunyady L (2012) Physiological mechanisms of signal termination in biological systems. Acta Physiol (Oxf) 204:469–478CrossRefGoogle Scholar
  15. 15.
    Kenakin T (2007) Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM receptors. Trends Pharmacol Sci 28:407–415PubMedCrossRefGoogle Scholar
  16. 16.
    Changeux JP (1964) Allosteric Interactions interpreted in terms of quaternary structure. Brookhaven Symp Biol 17:232–249PubMedGoogle Scholar
  17. 17.
    Kenakin T, Miller LJ (2010) Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 62:265–304PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Kenakin T (2004) Principles: receptor theory in pharmacology. Trends Pharmacol Sci 25:186–192PubMedCrossRefGoogle Scholar
  19. 19.
    Ghanouni P, Gryczynski Z, Steenhuis JJ et al (2001) Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta 2 adrenergic receptor. J Biol Chem 276:24433–24436PubMedCrossRefGoogle Scholar
  20. 20.
    Galandrin S, Bouvier M (2006) Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol Pharmacol 70:1575–1584PubMedCrossRefGoogle Scholar
  21. 21.
    Luttrell LM, Kenakin TP (2011) Refining efficacy: allosterism and bias in G protein-coupled receptor signaling. Methods Mol Biol 756:3–35PubMedCrossRefGoogle Scholar
  22. 22.
    Kenakin TP (2009) Cellular assays as portals to seven-transmembrane receptor-based drug discovery. Nat Rev Drug Discov 8:617–626PubMedCrossRefGoogle Scholar
  23. 23.
    Zhang R, Xie X (2012) Tools for GPCR drug discovery. Acta Pharmacol Sin 33:372–384PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Kenakin T, Christopoulos A (2013) Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat Rev Drug Discov 12:205–216PubMedCrossRefGoogle Scholar
  25. 25.
    Whalen EJ, Rajagopal S, Lefkowitz RJ (2011) Therapeutic potential of beta-arrestin- and G protein-biased agonists. Trends Mol Med 17:126–139PubMedCrossRefGoogle Scholar
  26. 26.
    Hill SJ, Ganellin CR, Timmerman H, Schwartz JC et al (1997) International union of pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 49:253–278PubMedGoogle Scholar
  27. 27.
    Powell JR, Brody MJ (1976) Identification and specific blockade of two receptors for histamine in the cardiovascular system. J Pharmacol Exp Ther 196:1–14PubMedGoogle Scholar
  28. 28.
    Black JW, Duncan WA, Durant CJ et al (1972) Definition and antagonism of histamine H2 -receptors. Nature 236:385–390PubMedCrossRefGoogle Scholar
  29. 29.
    Traiffort E, Pollard H, Moreau J et al (1992) Pharmacological characterization and autoradiographic localization of histamine H2 receptors in human brain identified with [125I]iodoaminopotentidine. J Neurochem 59:290–299PubMedCrossRefGoogle Scholar
  30. 30.
    Panula P, Chazot PL, Cowart M et al (2015) International union of basic and clinical pharmacology. XCVIII. Histamine receptors. Pharmacol Rev 67:601–655PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Alewijnse AE, Timmerman H, Jacobs EH et al (2000) The effect of mutations in the DRY motif on the constitutive activity and structural instability of the histamine H(2) receptor. Mol Pharmacol 57:890–898PubMedGoogle Scholar
  32. 32.
    Monczor F, Fernandez N, Legnazzi BL et al (2003) Tiotidine, a histamine H2 receptor inverse agonist that binds with high affinity to an inactive G-protein-coupled form of the receptor. Experimental support for the cubic ternary complex model. Mol Pharmacol 64:512–520PubMedCrossRefGoogle Scholar
  33. 33.
    Davio C, Mladovan A, Lemos B et al (2002) H1 and H2 histamine receptors mediate the production of inositol phosphates but not cAMP in human breast epithelial cells. Inflamm Res 51:1–7PubMedCrossRefGoogle Scholar
  34. 34.
    Traiffort E, Ruat M, Arrang JM et al (1992) Expression of a cloned rat histamine H2 receptor mediating inhibition of arachidonate release and activation of cAMP accumulation. Proc Natl Acad Sci U S A 89:2649–2653PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Bonini JS, Da Silva WC, Da Silveira CK et al (2011) Histamine facilitates consolidation of fear extinction. Int J Neuropsychopharmacol 14:1209–1217PubMedCrossRefGoogle Scholar
  36. 36.
    Kim NH, Lee AY (2010) Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival. Exp Dermatol 19:1073–1079PubMedCrossRefGoogle Scholar
  37. 37.
    Luo T, Chen B, Zhao Z et al (2013) Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function. Basic Res Cardiol 108:342PubMedCrossRefGoogle Scholar
  38. 38.
    Alonso N, Monczor F, Echeverria E et al (2014) Signal transduction mechanism of biased ligands at histamine H2 receptors. Biochem J 459:117–126PubMedCrossRefGoogle Scholar
  39. 39.
    Alonso N, Zappia CD, Cabrera M et al (2015) Physiological implications of biased signaling at histamine H2 receptors. Front Pharmacol 6:45PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Xu AJ, Kuramasu A, Maeda K et al (2008) Agonist-induced internalization of histamine H2 receptor and activation of extracellular signal-regulated kinases are dynamin-dependent. J Neurochem 107:208–217PubMedCrossRefGoogle Scholar
  41. 41.
    Mettler SE, Ghayouri S, Christensen GP et al (2007) Modulatory role of phosphoinositide 3-kinase in gastric acid secretion. Am J Physiol Gastrointest Liver Physiol 293:G532–G543PubMedCrossRefGoogle Scholar
  42. 42.
    Grandage VL, Gale RE, Linch DC et al (2005) PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, Mapkinase and p53 pathways. Leukemia 19:586–594PubMedGoogle Scholar
  43. 43.
    Min YH, Eom JI, Cheong JW et al (2003) Constitutive phosphorylation of Akt/PKB protein in acute myeloid leukemia: its significance as a prognostic variable. Leukemia 17:995–997PubMedCrossRefGoogle Scholar
  44. 44.
    Werner K, Neumann D, Seifert R (2016) High constitutive Akt2 activity in U937 promonocytes: effective reduction of Akt2 phosphorylation by the histamine H-receptor and the beta-adrenergic receptor. Naunyn Schmiedebergs Arch Pharmacol 389:87–101PubMedCrossRefGoogle Scholar
  45. 45.
    Aurelius J, Martner A, Brune M et al (2012) Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells. Haematologica 97:1904–1908PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Thoren FB, Romero AI, Brune M et al (2009) Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation immunotherapy in acute myeloid leukemia. Expert Opin Biol Ther 9:1217–1223PubMedCrossRefGoogle Scholar
  47. 47.
    Lemos Legnazzi B, Shayo C, Monczor F et al (2000) Rapid desensitization and slow recovery of the cyclic AMP response mediated by histamine H(2) receptors in the U937 cell line. Biochem Pharmacol 60:159–166PubMedCrossRefGoogle Scholar
  48. 48.
    Monczor F, Fernandez N, Riveiro E et al (2006) Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling. Biochem Pharmacol 71:1219–1228PubMedCrossRefGoogle Scholar
  49. 49.
    Shayo C, Legnazzi BL, Monczor F et al (2004) The time-course of cyclic AMP signaling is critical for leukemia U-937 cell differentiation. Biochem Biophys Res Commun 314:798–804PubMedCrossRefGoogle Scholar
  50. 50.
    Rodriguez-Pena MS, Timmerman H, Leurs R (2000) Modulation of histamine H(2) receptor signalling by G-protein-coupled receptor kinase 2 and 3. Br J Pharmacol 131:1707–1715PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Shayo C, Fernandez N, Legnazzi BL et al (2001) Histamine H2 receptor desensitization: involvement of a select array of G protein-coupled receptor kinases. Mol Pharmacol 60:1049–1056PubMedGoogle Scholar
  52. 52.
    Fernandez N, Monczor F, Lemos B et al (2002) Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation. Mol Pharmacol 62:1506–1514PubMedCrossRefGoogle Scholar
  53. 53.
    Fernandez N, Monczor F, Tubio MR et al (2007) Regulatory mechanisms underlying GKR2 levels in U937 cells: evidence for GRK3 involvement. Biochem Pharmacol 73:1758–1767PubMedCrossRefGoogle Scholar
  54. 54.
    Fernandez N, Gottardo FL, Alonso MN et al (2011) Roles of phosphorylation-dependent and -independent mechanisms in the regulation of histamine H2 receptor by G protein-coupled receptor kinase 2. J Biol Chem 286:28697–28706PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Fernandez N, Monczor F, Baldi A et al (2008) Histamine H2 receptor trafficking: role of arrestin, dynamin, and clathrin in histamine H2 receptor internalization. Mol Pharmacol 74:1109–1118PubMedCrossRefGoogle Scholar
  56. 56.
    Smit MJ, Timmerman H, Alewijnse AE et al (1995) Visualization of agonist-induced internalization of histamine H2 receptors. Biochem Biophys Res Commun 214:1138–1145PubMedCrossRefGoogle Scholar
  57. 57.
    Hershcovici T, Fass R (2011) Gastro-oesophageal reflux disease: beyond proton pump inhibitor therapy. Drugs 71:2381–2389PubMedCrossRefGoogle Scholar
  58. 58.
    Sigterman KE, van Pinxteren B, Bonis PA et al (2013) Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 5:CD002095Google Scholar
  59. 59.
    Sandler RS, Everhart JE, Donowitz M et al (2002) The burden of selected digestive diseases in the United States. Gastroenterology 122:1500–1511PubMedCrossRefGoogle Scholar
  60. 60.
    Marshall BJ, Goodwin CS, Warren JR et al (1988) Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter pylori. Lancet 2:1437–1442PubMedCrossRefGoogle Scholar
  61. 61.
    Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:1311–1315PubMedCrossRefGoogle Scholar
  62. 62.
    Olbe L, Carlsson E, Lindberg P (2003) A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov 2:132–139PubMedCrossRefGoogle Scholar
  63. 63.
    Laine L, Kivitz AJ, Bello AE et al (2012) Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers. Am J Gastroenterol 107:379–386PubMedCrossRefGoogle Scholar
  64. 64.
    Smit MJ, Leurs R, Alewijnse AE et al (1996) Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors. Proc Natl Acad Sci U S A 93:6802–6807PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Colucci R, Fleming JV, Xavier R et al (2001) L-histidine decarboxylase decreases its own transcription through downregulation of ERK activity. Am J Physiol Gastrointest Liver Physiol 281:G1081–G1091PubMedGoogle Scholar
  66. 66.
    Wessler S, Hocker M, Fischer W et al (2000) Helicobacter pylori activates the histidine decarboxylase promoter through a mitogen-activated protein kinase pathway independent of pathogenicity island-encoded virulence factors. J Biol Chem 275:3629–3636PubMedCrossRefGoogle Scholar
  67. 67.
    Reher TM, Brunskole I, Neumann D et al (2012) Evidence for ligand-specific conformations of the histamine H(2)-receptor in human eosinophils and neutrophils. Biochem Pharmacol 84:1174–1185PubMedCrossRefGoogle Scholar
  68. 68.
    Martner A, Thoren FB, Aurelius J et al (2010) Immunotherapy with histamine dihydrochloride for the prevention of relapse in acute myeloid leukemia. Expert Rev Hematol 3:381–391PubMedCrossRefGoogle Scholar
  69. 69.
    Burde R, Buschauer A, Seifert R (1990) 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 341:455–461PubMedCrossRefGoogle Scholar
  70. 70.
    Burde R, Seifert R, Buschauer A et al (1989) Histamine inhibits activation of human neutrophils and HL-60 leukemic cells via H2-receptors. Naunyn Schmiedebergs Arch Pharmacol 340:671–678PubMedCrossRefGoogle Scholar
  71. 71.
    Copsel S, Garcia C, Diez F et al (2011) Multidrug resistance protein 4 (MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cell proliferation and differentiation. J Biol Chem 286:6979–6988PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Jutel M, Akdis M, Akdis CA (2009) Histamine, histamine receptors and their role in immune pathology. Clin Exp Allergy 39:1786–1800PubMedCrossRefGoogle Scholar
  73. 73.
    Seifert R, Hoer A, Schwaner I et al (1992) Histamine increases cytosolic Ca2+ in HL-60 promyelocytes predominantly via H2 receptors with an unique agonist/antagonist profile and induces functional differentiation. Mol Pharmacol 42:235–241PubMedGoogle Scholar
  74. 74.
    Pearce FL (1991) Biological effects of histamine: an overview. Agents Actions 33:4–7PubMedCrossRefGoogle Scholar
  75. 75.
    Jutel M, Blaser K, Akdis CA (2006) The role of histamine in regulation of immune responses. Chem Immunol Allergy 91:174–187PubMedCrossRefGoogle Scholar
  76. 76.
    Hellstrand K, Asea A, Dahlgren C et al (1994) Histaminergic regulation of NK cells. Role of monocyte-derived reactive oxygen metabolites. J Immunol 153:4940–4947PubMedGoogle Scholar
  77. 77.
    Ching TL, Koelemij JG, Bast A (1995) The effect of histamine on the oxidative burst of HL60 cells before and after exposure to reactive oxygen species. Inflamm Res 44:99–104PubMedCrossRefGoogle Scholar
  78. 78.
    Malmberg KJ (2004) Effective immunotherapy against cancer: a question of overcoming immune suppression and immune escape? Cancer Immunol Immunother 53:879–892PubMedCrossRefGoogle Scholar
  79. 79.
    Murdoch C, Giannoudis A, Lewis CE (2004) Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 104:2224–2234PubMedCrossRefGoogle Scholar
  80. 80.
    Hellstrand K (2002) Histamine in cancer immunotherapy: a preclinical background. Semin Oncol 29:35–40PubMedCrossRefGoogle Scholar
  81. 81.
    Kenakin TP, Ambrose JR, Irving PE (1991) The relative efficiency of beta adrenoceptor coupling to myocardial inotropy and diastolic relaxation: organ-selective treatment for diastolic dysfunction. J Pharmacol Exp Ther 257:1189–1197PubMedGoogle Scholar
  82. 82.
    Hahm KB, Park IS, Kim HC et al (1996) Comparison of antiproliferative effects of 1-histamine-2 receptor antagonists, cimetidine, ranitidine, and famotidine, in gastric cancer cells. Int J Immunopharmacol 18:393–399PubMedCrossRefGoogle Scholar
  83. 83.
    Diebel LN, Liberati DM, Hall-Zimmerman L (2011) H2 blockers decrease gut mucus production and lead to barrier dysfunction in vitro. Surgery 150:736–743PubMedCrossRefGoogle Scholar
  84. 84.
    Cianchi F, Cortesini C, Schiavone N et al (2005) 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 11:6807–6815PubMedCrossRefGoogle Scholar
  85. 85.
    Fujimoto S, Komine M, Karakawa M et al (2011) Histamine differentially regulates the production of Th1 and Th2 chemokines by keratinocytes through histamine H1 receptor. Cytokine 54:191–199PubMedCrossRefGoogle Scholar
  86. 86.
    de Lera RM, Zheng J, Berlin MY et al (2013) Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor antagonists for the treatment of obesity. Bioorg Med Chem Lett 23:6004–6009CrossRefGoogle Scholar
  87. 87.
    Muller T, Myrtek D, Bayer H et al (2006) Functional characterization of histamine receptor subtypes in a human bronchial epithelial cell line. Int J Mol Med 18:925–931PubMedGoogle Scholar
  88. 88.
    Pagotto RM, Monzon C, Moreno MB et al (2012) Proliferative effect of histamine on MA-10 Leydig tumor cells mediated through HRH2 activation, transient elevation in cAMP production, and increased extracellular signal-regulated kinase phosphorylation levels. Biol Reprod 87:150PubMedCrossRefGoogle Scholar
  89. 89.
    Martinel Lamas DJ, Cortina JE, Ventura C et al (2015) Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer. Cancer Biol Ther 16:137–148PubMedCrossRefGoogle Scholar
  90. 90.
    Porretti JC, Mohamad NA, Martin GA et al (2014) Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells which is prevented by fibroblasts treatment with histamine in high concentration. Int J Biochem Cell Biol 51:29–38PubMedCrossRefGoogle Scholar
  91. 91.
    Davio C, Baldi A, Shayo C et al (1995) H1 and H2 histamine receptors in histiocytic lymphoma cell line U-937. Inflamm Res 44(S1):S72–S73PubMedCrossRefGoogle Scholar
  92. 92.
    Nagai Y, Tanaka Y, Kuroishi et al (2012) Histamine reduces susceptibility to natural killer cells via down-regulation of NKG2D ligands on human monocytic leukaemia THP-1 cells. Immunology 136:103-114Google Scholar
  93. 93.
    Tanimoto A, Murata Y, Nomaguchi M et al (2001) Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells. FEBS Lett 508:345–349PubMedCrossRefGoogle Scholar
  94. 94.
    Brodsky A, Davio C, Shayo C et al (1998) Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation. Eur J Pharmacol 350:121–127PubMedCrossRefGoogle Scholar
  95. 95.
    Shayo C, Davio C, Brodsky A et al (1997) Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937. Mol Pharmacol 51:983–990PubMedGoogle Scholar
  96. 96.
    Mitsuhashi M, Payan DG (1991) Multiple signaling pathways of histamine H2 receptors. Agents Actions 33:289–294PubMedGoogle Scholar
  97. 97.
    Cho EJ, An HJ, Shin JS et al (2011) Roxatidine suppresses inflammatory responses via inhibition of NF-kappaB and p38 MAPK activation in LPS-induced RAW 264.7 macrophages. J Cell Biochem 112:3648–3659PubMedCrossRefGoogle Scholar
  98. 98.
    Kimura S, Wang KY, Yamada S et al (2015) CCL22/Macrophage-derived chemokine expression in apolipoprotein e-deficient mice and effects of histamine in the setting of atherosclerosis. J Atheroscler Thromb 22:599–609PubMedCrossRefGoogle Scholar
  99. 99.
    Mirzahosseini A, Kovacs M, Kanai K et al (2015) BODIPY((R)) FL histamine as a new modality for quantitative detection of histamine receptor upregulation upon IgE sensitization in murine bone marrow-derived mast cells. Cytometry A 87:23–31PubMedCrossRefGoogle Scholar
  100. 100.
    Alonso N, Fernandez N, Notcovich C et al (2013) Cross-desensitization and cointernalization of H1 and H2 histamine receptors reveal new insights into histamine signal integration. Mol Pharmacol 83:1087–1098PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Shen Y, Hu WW, Fan YY et al (2007) Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H(1)/H(3) receptors. Biochem Pharmacol 73:709–717PubMedCrossRefGoogle Scholar
  102. 102.
    Wu T, Gan X, Zhou S et al (2013) Histamine at low concentrations aggravates rat liver BRL-3A cell injury induced by hypoxia/reoxygenation through histamine H2 receptor in vitro. Toxicol In Vitro 27:378–386PubMedCrossRefGoogle Scholar
  103. 103.
    Hadri L, Pavoine C, Lipskaia L et al (2006) Transcription of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase type 3 gene, ATP2A3, is regulated by the calcineurin/NFAT pathway in endothelial cells. Biochem J 394:27–33PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Huwiler A, Doll F, Ren S et al (2006) Histamine increases sphingosine kinase-1 expression and activity in the human arterial endothelial cell line EA.hy 926 by a PKC-alpha-dependent mechanism. Biochim Biophys Acta 1761:367–376PubMedCrossRefGoogle Scholar
  105. 105.
    Cricco G, Martin G, Medina V et al (2006) Histamine inhibits cell proliferation and modulates the expression of Bcl-2 family proteins via the H2 receptor in human pancreatic cancer cells. Anticancer Res 26:4443–4450PubMedGoogle Scholar
  106. 106.
    Ramos-Jimenez J, Soria-Jasso LE, Lopez-Colombo A et al (2007) Histamine augments beta2-adrenoceptor-induced cyclic AMP accumulation in human prostate cancer cells DU-145 independently of known histamine receptors. Biochem Pharmacol 73:814–823PubMedCrossRefGoogle Scholar
  107. 107.
    Hiller C, Kuhhorn J, Gmeiner P (2013) Class A G-protein-coupled receptor (GPCR) dimers and bivalent ligands. J Med Chem 56:6542–6559PubMedCrossRefGoogle Scholar
  108. 108.
    Schmitt JM, Stork PJ (2000) beta 2-adrenergic receptor activates extracellular signal-regulated kinases (ERKs) via the small G protein rap1 and the serine/threonine kinase B-Raf. J Biol Chem 275:25342–25350PubMedCrossRefGoogle Scholar
  109. 109.
    Shaw G, Morse S, Ararat M et al (2002) Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells. FASEB J 16:869–871PubMedGoogle Scholar
  110. 110.
    Smit MJ, Timmerman H, Blauw J et al (1996) The C terminal tail of the histamine H2 receptor contains positive and negative signals important for signal transduction and receptor down-regulation. J Neurochem 67:1791–1800PubMedCrossRefGoogle Scholar
  111. 111.
    Milligan G (2003) Principles: extending the utility of [35S]GTP gamma S binding assays. Trends Pharmacol Sci 24:87–90PubMedCrossRefGoogle Scholar
  112. 112.
    Labrecque J, Wong RS, Fricker SP (2009) A time-resolved fluorescent lanthanide (Eu)-GTP binding assay for chemokine receptors as targets in drug discovery. Methods Mol Biol 552:153–169PubMedCrossRefGoogle Scholar
  113. 113.
    Davio CA, Cricco GP, Bergoc RM et al (1995) H1 and H2 histamine receptors in N-nitroso-N-methylurea (NMU)-induced carcinomas with atypical coupling to signal transducers. Biochem Pharmacol 50:91–96PubMedCrossRefGoogle Scholar
  114. 114.
    Berridge MJ (1993) Inositol trisphosphate and calcium signalling. Nature 361:315–325PubMedCrossRefGoogle Scholar
  115. 115.
    Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450PubMedGoogle Scholar
  116. 116.
    Pitcher J, Lohse MJ, Codina J et al (1992) Desensitization of the isolated beta 2-adrenergic receptor by beta-adrenergic receptor kinase, cAMP-dependent protein kinase, and protein kinase C occurs via distinct molecular mechanisms. Biochemistry 31:3193–3197PubMedCrossRefGoogle Scholar
  117. 117.
    Lohse MJ, Andexinger S, Pitcher J et al (1992) Receptor-specific desensitization with purified proteins. Kinase dependence and receptor specificity of beta-arrestin and arrestin in the beta 2-adrenergic receptor and rhodopsin systems. J Biol Chem 267:8558–8564PubMedGoogle Scholar
  118. 118.
    Kim J, Ahn S, Ren XR et al (2005) Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signaling. Proc Natl Acad Sci U S A 102:1442–1447PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Ren XR, Reiter E, Ahn S et al (2005) Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor. Proc Natl Acad Sci U S A 102:1448–1453PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Zidar DA, Violin JD, Whalen EJ et al (2009) Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands. Proc Natl Acad Sci U S A 106:9649–9654PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Liggett SB (2011) Phosphorylation barcoding as a mechanism of directing GPCR signaling. Sci Signal 4:pe36PubMedCrossRefGoogle Scholar
  122. 122.
    Oakley RH, Laporte SA, Holt JA et al (1999) Association of beta-arrestin with G protein-coupled receptors during clathrin-mediated endocytosis dictates the profile of receptor resensitization. J Biol Chem 274:32248–32257PubMedCrossRefGoogle Scholar
  123. 123.
    Sever S (2002) Dynamin and endocytosis. Curr Opin Cell Biol 14:463–467PubMedCrossRefGoogle Scholar
  124. 124.
    Tsao P, Cao T, von Zastrow M (2001) Role of endocytosis in mediating downregulation of G-protein-coupled receptors. Trends Pharmacol Sci 22:91–96PubMedCrossRefGoogle Scholar
  125. 125.
    Prossnitz ER (2004) Novel roles for arrestins in the post-endocytic trafficking of G protein-coupled receptors. Life Sci 75:893–899PubMedCrossRefGoogle Scholar
  126. 126.
    Chabre M, le Maire M (2005) Monomeric G-protein-coupled receptor as a functional unit. Biochemistry 44:9395–9403PubMedCrossRefGoogle Scholar
  127. 127.
    Gurevich VV, Gurevich EV (2008) GPCR monomers and oligomers: it takes all kinds. Trends Neurosci 31:74–81PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Bulenger S, Marullo S, Bouvier M (2005) Emerging role of homo- and heterodimerization in G-protein-coupled receptor biosynthesis and maturation. Trends Pharmacol Sci 26:131–137PubMedCrossRefGoogle Scholar
  129. 129.
    Terrillon S, Bouvier M (2004) Roles of G-protein-coupled receptor dimerization. EMBO Rep 5:30–34PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Lohse MJ, Nuber S, Hoffmann C (2012) Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling. Pharmacol Rev 64:299–336PubMedCrossRefGoogle Scholar
  131. 131.
    Milligan G, Ramsay D, Pascal G et al (2003) GPCR dimerisation. Life Sci 74:181–188PubMedCrossRefGoogle Scholar
  132. 132.
    Youvan DC, Silva CM, Bylina EJ, Coleman WJ et al (1997) Calibration of fluorescence resonance energy transfer in microscopy using genetically engineered GFP derivatives on nickel chelating beads. Biotechnol Alia 3:1–18Google Scholar
  133. 133.
    Luttrell LM (2014) Minireview: more than just a hammer: ligand “bias” and pharmaceutical discovery. Mol Endocrinol 28:281–294PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Haasen D, Wolff M, Valler MJ et al (2006) Comparison of G-protein coupled receptor desensitization-related beta-arrestin redistribution using confocal and non-confocal imaging. Comb Chem High Throughput Screen 9:37–47PubMedCrossRefGoogle Scholar
  135. 135.
    Kamal M, Marquez M, Vauthier V et al (2009) Improved donor/acceptor BRET couples for monitoring beta-arrestin recruitment to G protein-coupled receptors. Biotechnol J 4:1337–1344PubMedCrossRefGoogle Scholar
  136. 136.
    Barnea G, Strapps W, Herrada G et al (2008) The genetic design of signaling cascades to record receptor activation. Proc Natl Acad Sci U S A 105:64–69PubMedCrossRefGoogle Scholar
  137. 137.
    Wetter JA, Revankar C, Hanson BJ (2009) Utilization of the Tango beta-arrestin recruitment technology for cell-based EDG receptor assay development and interrogation. J Biomol Screen 14:1134–1141PubMedCrossRefGoogle Scholar
  138. 138.
    Yin H, Chu A, Li W et al (2009) Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. J Biol Chem 284:12328–12338PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Rajagopal S, Rajagopal K, Lefkowitz RJ (2010) Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat Rev Drug Discov 9:373–386PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Chen D, Aihara T, Zhao CM et al (2006) Differentiation of the gastric mucosa. I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes. Am J Physiol 291:G539–G544Google Scholar
  141. 141.
    Gschwandtner M, Bunk H, Kother B et al (2012) Histamine down-regulates IL-27 production in antigen-presenting cells. J Leukoc Biol 92:21–29PubMedCrossRefGoogle Scholar
  142. 142.
    Gutzmer R, Langer K, Lisewski M et al (2002) Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells. J Allergy Clin Immunol 109:524–531PubMedCrossRefGoogle Scholar
  143. 143.
    Hegyesi H, Horvath B, Pallinger E et al (2005) Histamine elevates the expression of Ets-1, a protooncogen in human melanoma cell lines through H2 receptor. FEBS Lett 579:2475–2479PubMedCrossRefGoogle Scholar
  144. 144.
    Lee CL, Hsu SH, Jong YJ et al (2013) Inhibition of histamine H1 receptor activity modulates proinflammatory cytokine production of dendritic cells through c-Rel activity. Int Arch Allergy Immunol 160:265–274PubMedCrossRefGoogle Scholar
  145. 145.
    Barlow RB, Scott KA, Stephenson RP (1963) An attempt to study the effects of chemical structure on the affinity and efficacy of compounds related to acetylcholine. Br J Pharmacol Chemother 21:509–522PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Rajagopal S, Ahn S, Rominger DH et al (2011) Quantifying ligand bias at seven-transmembrane receptors. Mol Pharmacol 80:367–377PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Colquhoun D (1985) Imprecision in presentation of binding studies. Trends Pharmacol Sci 6:197CrossRefGoogle Scholar
  148. 148.
    McLoughlin DJ, Strange PG (2000) Mechanisms of agonism and inverse agonism at serotonin 5-HT1A receptors. J Neurochem 74:347–357PubMedCrossRefGoogle Scholar
  149. 149.
    McPherson J, Rivero G, Baptist M et al (2010) mu-opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization. Mol Pharmacol 78:756–766PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Rasmussen SG, DeVree BT, Zou Y et al (2011) Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477:549–555PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Clarke WP, Bond RA (1998) The elusive nature of intrinsic efficacy. Trends Pharmacol Sci 19:270–276PubMedCrossRefGoogle Scholar
  152. 152.
    Kenakin T, Watson C, Muniz-Medina V et al (2012) A simple method for quantifying functional selectivity and agonist bias. ACS Chem Nerosci 3:193–203CrossRefGoogle Scholar
  153. 153.
    Thompson GL, Lane JR, Coudrat T et al (2015) Biased agonism of endogenous opioid peptides at the mu-opioid receptor. Mol Pharmacol 88:335–346PubMedCrossRefGoogle Scholar
  154. 154.
    Shenoy SK, Lefkowitz RJ (2011) beta-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci 32:521–533PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Natalia C. Fernández
    • 1
    Email author
  • Carina Shayo
    • 2
  • Carlos Davio
    • 1
  • Federico Monczor
    • 1
  1. 1.Instituto de Investigaciones Farmacológicas, Facultad de Farmacia y BioquímicaININFA-UBA-CONICETCiudad Autónoma de Buenos AiresArgentina
  2. 2.Instituto de Biología y Medicina ExperimentalIByME-CONICETCiudad Autónoma de Buenos AiresArgentina

Personalised recommendations