BioPAX pathway converted from "Histamine receptors" in the Reactome database. Histamine receptors Histamine receptors This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> HRH1 binds hist HRH1 binds hist This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 9800241 1 plasma membrane GO 0005886 UniProt:P70174 Hrh1 Reactome http://www.reactome.org Mus musculus NCBI Taxonomy 10090 UniProt P70174 Chain Coordinates 1 EQUAL 487 EQUAL Reactome DB_ID: 390899 1 extracellular region GO 0005576 histaminium [ChEBI:58432] histaminium histamine 2-(1H-imidazol-4-yl)ethanaminium histaminium cation ChEBI 58432 Reactome DB_ID: 9800243 1 HRH1:Hist [plasma membrane] HRH1:Hist Reactome DB_ID: 9800241 1 1 EQUAL 487 EQUAL Reactome DB_ID: 390899 1 Reactome Database ID Release 81 9800243 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9800243 Reactome R-MMU-390885 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-390885.1 Reactome Database ID Release 81 9802912 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9802912 Reactome R-MMU-390912 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-390912.1 The histamine H1 receptor (De Backer MD et al, 1993) is found on smooth muscle, endothelium and the CNS. Histamine released from neurons binds to the H1 receptor and causes systemic vasodilation and increased endothelial cell permeability. The effects are modulated by the activated receptor binding to the G protein alpha-q/11 subtype which can activate phospholipase C and the phosphatidylinositol (PIP2) signaling pathway (Tilly BC et al, 1990). The classical antihistamines (histamine H1 receptor antagonists) were developed in the early 1930s and were shown to reduce the effects of histamine on many tissues. 2155607 Pubmed 1990 Histamine-H1-receptor-mediated phosphoinositide hydrolysis, Ca2+ signalling and membrane-potential oscillations in human HeLa carcinoma cells Tilly, BC Tertoolen, LG Lambrechts, AC Remorie, R de Laat, SW Moolenaar, WH Biochem J 266:235-43 8280179 Pubmed 1993 Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor De Backer, MD Gommeren, W Moereels, H Nobels, G Van Gompel, P Leysen, JE Luyten, WH Biochem Biophys Res Commun 197:1601-8 inferred by electronic annotation IEA GO IEA HRH1 binds HRH1 inverse agonists HRH1 binds HRH1 inverse agonists This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 9692532 1 HRH1 inverse agonists [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity haloperidol [extracellular region] mizolastine [extracellular region] asenapine [extracellular region] promethazine [extracellular region] alimemazine [extracellular region] cyclizine [extracellular region] cyproheptadine [extracellular region] epinastine [extracellular region] ketotifen [extracellular region] clemastine [extracellular region] tripelennamine [extracellular region] cetirizine [extracellular region] terfenadine [extracellular region] fexofenadine [extracellular region] triprolidine [extracellular region] thiothixene [extracellular region] mepyramine [extracellular region] desloratadine [extracellular region] clozapine [extracellular region] diphenhydramine [extracellular region] perphenazine [extracellular region] ziprasidone [extracellular region] chlorpromazine [extracellular region] quetiapine [extracellular region] hydroxyzine [extracellular region] thioridazine [extracellular region] pitolisant [extracellular region] molindone [extracellular region] olanzapine [extracellular region] azelastine [extracellular region] trifluoperazine [extracellular region] fluspirilene [extracellular region] doxepin [extracellular region] amitriptyline [extracellular region] dosulepin [extracellular region] fluphenazine [extracellular region] loxapine [extracellular region] rupatadine [extracellular region] astemizole [extracellular region] loratadine [extracellular region] bilastine [extracellular region] chlorpheniramine [extracellular region] aripiprazole [extracellular region] Guide to Pharmacology 86 Guide to Pharmacology 10102 Guide to Pharmacology 22 Guide to Pharmacology 7282 Guide to Pharmacology 7237 Guide to Pharmacology 7151 Guide to Pharmacology 277 Guide to Pharmacology 7176 Guide to Pharmacology 7206 Guide to Pharmacology 6063 Guide to Pharmacology 7318 Guide to Pharmacology 1222 Guide to Pharmacology 2608 Guide to Pharmacology 4819 Guide to Pharmacology 1228 Guide to Pharmacology 212 Guide to Pharmacology 1227 Guide to Pharmacology 7157 Guide to Pharmacology 38 Guide to Pharmacology 1224 Guide to Pharmacology 209 Guide to Pharmacology 59 Guide to Pharmacology 83 Guide to Pharmacology 50 Guide to Pharmacology 7199 Guide to Pharmacology 100 Guide to Pharmacology 8924 Guide to Pharmacology 207 Guide to Pharmacology 47 Guide to Pharmacology 7121 Guide to Pharmacology 214 Guide to Pharmacology 85 Guide to Pharmacology 1225 Guide to Pharmacology 200 Guide to Pharmacology 7549 Guide to Pharmacology 204 Guide to Pharmacology 205 Guide to Pharmacology 10103 Guide to Pharmacology 2603 Guide to Pharmacology 7216 Guide to Pharmacology 11579 Guide to Pharmacology 6976 Guide to Pharmacology 34 Reactome DB_ID: 9800241 1 1 EQUAL 487 EQUAL Reactome DB_ID: 9881129 1 HRH1:HRH1 inverse agonists [plasma membrane] HRH1:HRH1 inverse agonists Converted from EntitySet in Reactome Reactome DB_ID: 9692532 1 Reactome DB_ID: 9800241 1 1 EQUAL 487 EQUAL Reactome Database ID Release 81 9881129 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881129 Reactome R-MMU-9692576 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692576.1 Reactome Database ID Release 81 9881131 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881131 Reactome R-MMU-9692539 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692539.1 Histamine is a biogenic amine involved in local immune responses, regulation of gut function and neurotransmission. It exerts its actions by binding to one of four human histamine receptors (HRHs). They belong to the family of rhodopsin-like G-protein-coupled receptors (Panula et al. 2015). Histamine binding to HRHs brings about many physiologic changes, including neurotransmission, inflammation, smooth muscle contraction, dilatation of capillaries, chemotaxis, cytokine production and gastric acid secretion. The histamine H1 receptor (HRH1) is found on smooth muscle and the vascular endothelium, and in the heart and the CNS. Histamine released from neurons binds to HRH1 and causes systemic vasodilation and increased endothelial cell permeability. HRH1 displays constitutive receptor activation in the absence of agonists (Bakker et al. 2000).<br><br>More than 40 HRH1 antihistamines are available worldwide, comprising the largest class of medications used in the treatment of allergic diseases. For more than 50 years these drugs were thought to act as antagonists of HRH1 but it is now known that most of these drugs act as inverse agonists that combine with and stabilize the inactive conformation of HRH1, shifting the equilibrium toward the inactive state (Bakker et al. 2000, Nijmeijer et al. 2010). HRH1 antihistamines are functionally classified as first (old) generation and second (new) generation. First (old)–generation HRH1 antihistamines may cross the blood-brain barrier and interfere with neurotransmission in the CNS, with adverse affects, even resulting in death in overdose cases. First-generation HRH1 antihistamines include chlorpheniramine, diphenhydramine and hydroxyzine, amongst others. Second (new)–generation HRH1 antihistamines are used to treat allergic rhinitis, allergic conjunctivitis, and urticaria. These drugs minimally cross the blood-brain barrier and do not impair alertness, learning, memory, or multitasking and are minimally sedative. Overdose does not cause toxicity or death. Second-generation HRH1 antihistamines include bilastine, ceterizine, fexofenadine, loratadine and reupatadine, amongst others (Yanai et al. 2012, Simons & Akdis 2014, Fein et al. 2019). 978-0-323-08593-9 ISBN 2014 94 - Histamine and H1 Antihistamines Simons, Estelle Akdis, Cesmi Middleton's Allergy (Eighth Edition) (Book): 1503-1533 31582993 Pubmed 2019 CSACI position statement: Newer generation H<sub>1</sub>-antihistamines are safer than first-generation H<sub>1</sub>-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria Fein, Michael N Fischer, David A O'Keefe, Andrew W Sussman, Gord L Allergy Asthma Clin Immunol 15:61 26084539 Pubmed 2015 International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors Panula, Pertti Chazot, Paul L Cowart, Marlon Gutzmer, Ralf Leurs, Rob Liu, Wai L S Stark, Holger Thurmond, Robin L Haas, Helmut L Pharmacol. Rev. 67:601-55 10633171 Pubmed 2000 Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H(1) receptor antagonists Bakker, R A Wieland, K Timmerman, H Leurs, R Eur. J. Pharmacol. 387:R5-7 21036230 Pubmed 2010 Constitutive activity of the histamine H(1) receptor Nijmeijer, Saskia Leurs, Rob Vischer, Henry F Meth. Enzymol. 484:127-47 22455874 Pubmed 2012 Safety considerations in the management of allergic diseases: focus on antihistamines Yanai, K Rogala, B Chugh, K Paraskakis, E Pampura, A N Boev, R Curr Med Res Opin 28:623-42 inferred by electronic annotation IEA GO IEA HRH2 binds hist HRH2 binds hist This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 390899 1 Reactome DB_ID: 9799728 1 UniProt:P97292 Hrh2 UniProt P97292 1 EQUAL 359 EQUAL Reactome DB_ID: 9799730 1 HRH2:histamine [plasma membrane] HRH2:histamine Reactome DB_ID: 390899 1 Reactome DB_ID: 9799728 1 1 EQUAL 359 EQUAL Reactome Database ID Release 81 9799730 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9799730 Reactome R-MMU-390881 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-390881.1 Reactome Database ID Release 81 9802910 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9802910 Reactome R-MMU-390909 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-390909.1 Histamine H2 receptors (Gantz I et al, 1991) are primarily located on parietal cells (oxyntic cells) which are the stomach epithelium cells that secrete gastric acid in response to histamine. This action is modulated by coupling of the activated receptor with the G protein alpha-s subtype which can stimulate adenylate cyclase (Mitsuhashi M et al, 1989). Through a separate mechanism, the activated receptor can also couple with the G protein alpha-q/11 to stimulate phospholipase C (Mitsuhashi M et al, 1989). H2-receptor antagonists (H2RA) are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells.They are used in the treatment of dyspepsia. 2553705 Pubmed 1989 Multiple signaling pathways of histamine H2 receptors. Identification of an H2 receptor-dependent Ca2+ mobilization pathway in human HL-60 promyelocytic leukemia cells Mitsuhashi, M Mitsuhashi, T Payan, DG J Biol Chem 264:18356-62 1714721 Pubmed 1991 Molecular cloning of the human histamine H2 receptor Gantz, I Munzert, G Tashiro, T Schäffer, M Wang, L DelValle, J Yamada, T Biochem Biophys Res Commun 178:1386-92 inferred by electronic annotation IEA GO IEA HRH2 binds HRH2 antagonists HRH2 binds HRH2 antagonists This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 9692737 1 HRH2 antagonists [extracellular region] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CIM [extracellular region] ranitidine [extracellular region] nizatidine [extracellular region] famotidine [extracellular region] Guide to Pharmacology 1231 Guide to Pharmacology 1234 Guide to Pharmacology 7248 Guide to Pharmacology 7074 Reactome DB_ID: 9799728 1 1 EQUAL 359 EQUAL Reactome DB_ID: 9881133 1 HRH2:HRH2 antagonists [plasma membrane] HRH2:HRH2 antagonists Converted from EntitySet in Reactome Reactome DB_ID: 9692737 1 Reactome DB_ID: 9799728 1 1 EQUAL 359 EQUAL Reactome Database ID Release 81 9881133 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881133 Reactome R-MMU-9692725 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692725.1 Reactome Database ID Release 81 9881135 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881135 Reactome R-MMU-9692738 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692738.1 When bound to its endogenous ligand histamine, the histamine H2 receptor (HRH2) mediates mediates gastric acid secretion, gastrointestinal motility and intestinal secretion. HRH2 is also thought to be involved in regulating cell growth and differentiation (Panula et al. 2015). The HRH2 antagonists cimetidine (Black et al. 1972, Ganellin 1981), ranitidine (Brogden et al. 1982), nizatidine (Price & Brogden 1988) and famotidine (Campoli-Richards & Clissold 1986) are well established treatments (Baker et al. 2008) for patients presenting with dyspepsia, gastric or duodenal ulcers, or gastroesophageal reflux disease (Sigterman et al. 2013). 4401751 Pubmed 1972 Definition and antagonism of histamine H 2 -receptors BLACK, J W Duncan, W A Durant, C J Ganellin, C R Parsons, E M Nature 236:385-90 6128216 Pubmed 1982 Ranitidine: a review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases Brogden, R N Carmine, A A Heel, R C Speight, T M Avery, G S Drugs 24:267-303 18157166 Pubmed 2008 A study of antagonist affinities for the human histamine H2 receptor Baker, J G Br. J. Pharmacol. 153:1011-21 6120235 Pubmed 1981 1980 Award in Medicinal Chemistry: Medicinal chemistry and dynamic structure-activity analysis in the discovery of drugs acting at histamine H2 receptors Ganellin, R J. Med. Chem. 24:913-20 2875864 Pubmed 1986 Famotidine. Pharmacodynamic and pharmacokinetic properties and a preliminary review of its therapeutic use in peptic ulcer disease and Zollinger-Ellison syndrome Campoli-Richards, D M Clissold, S P Drugs 32:197-221 9311023 Pubmed 1997 International Union of Pharmacology. XIII. Classification of histamine receptors Hill, SJ Ganellin, CR Timmerman, H Schwartz, JC Shankley, NP Young, JM Schunack, W Levi, R Haas, HL Pharmacol Rev 49:253-78 23728637 Pubmed 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 Sigterman, Kirsten E van Pinxteren, Bart Bonis, Peter A Lau, Joseph Numans, Mattijs E Cochrane Database Syst RevCD002095 2905640 Pubmed 1988 Nizatidine. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease Price, A H Brogden, R N Drugs 36:521-39 inferred by electronic annotation IEA GO IEA HRH3 binds Hist HRH3 binds Hist This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 9881149 1 UniProt:P58406 Hrh3 UniProt P58406 1 EQUAL 445 EQUAL Reactome DB_ID: 390899 1 Reactome DB_ID: 9881155 1 HRH3:Hist [plasma membrane] HRH3:Hist Reactome DB_ID: 9881149 1 1 EQUAL 445 EQUAL Reactome DB_ID: 390899 1 Reactome Database ID Release 81 9881155 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881155 Reactome R-MMU-9692866 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692866.1 Reactome Database ID Release 81 9881157 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881157 Reactome R-MMU-9692880 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692880.1 Histamine H3 receptor (HRH3) (Lovenberg et al. 1999) is predominantly expressed in the CNS and is involved in decreasing the release of neurotransmitters such as histamine, acetylcholine, norepinephrine and serotonin. There are currently at least six isoforms of the H3 receptor in humans of which isoforms 1,2 and 4 encode functional proteins (Wellendorph et al. 2002). 12069903 Pubmed 2002 Molecular cloning and pharmacology of functionally distinct isoforms of the human histamine H(3) receptor Wellendorph, P Goodman, MW Burstein, ES Nash, NR Brann, MR Weiner, DM Neuropharmacology 42:929-40 10347254 Pubmed 1999 Cloning and functional expression of the human histamine H3 receptor Lovenberg, TW Roland, BL Wilson, SJ Jiang, X Pyati, J Huvar, A Jackson, MR Erlander, MG Mol Pharmacol 55:1101-7 inferred by electronic annotation IEA GO IEA HRH3 binds pitosilant HRH3 binds pitosilant This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 9881149 1 1 EQUAL 445 EQUAL Reactome DB_ID: 9692536 1 pitolisant [Guide to Pharmacology:8924] pitolisant Wakix&reg; tiprolisant [USAN] BF2.649 Reactome DB_ID: 9881151 1 HRH3:pitosilant [plasma membrane] HRH3:pitosilant Reactome DB_ID: 9881149 1 1 EQUAL 445 EQUAL Reactome DB_ID: 9692536 1 Reactome Database ID Release 81 9881151 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881151 Reactome R-MMU-9692855 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692855.1 Reactome Database ID Release 81 9881153 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9881153 Reactome R-MMU-9692867 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-9692867.1 The histamine H3 receptors (HRH3) mediate the histamine signals in the CNS and peripheral nervous system. It signals through the inhibition of adenylate cyclase and displays high constitutive activity. It functions as an auto- and a hetero-receptor at pre- and post-synaptic membranes and has a profound influence on different neurotransmitter balances (Arrang et al. 1983).<br><br>Pitolisant is a selective inverse/agonist/antagonist of HRH3 (Ligneau et al. 2007) and is used to treat type 1 or 2 narcolepsy (Dauvilliers et al. 2013). 6188956 Pubmed 1983 Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor Arrang, J M Garbarg, M Schwartz, J C Nature 302:832-7 17005916 Pubmed 2007 BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology Ligneau, X Perrin, D Landais, L Camelin, J-C Calmels, T P G Berrebi-Bertrand, I Lecomte, J-M Parmentier, R Anaclet, C Lin, J-S Bertaina-Anglade, V la Rochelle, C Drieu d'Aniello, F Rouleau, A Gbahou, F Arrang, J-M Ganellin, C R Stark, H Schunack, W Schwartz, J-C J. Pharmacol. Exp. Ther. 320:365-75 24107292 Pubmed 2013 Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial Dauvilliers, Yves Bassetti, Claudio Lammers, Gert Jan Arnulf, Isabelle Mayer, Geert Rodenbeck, Andrea Lehert, Philippe Ding, Claire-Li Lecomte, Jeanne-Marie Schwartz, Jean-Charles HARMONY I study group, - Lancet Neurol 12:1068-75 inferred by electronic annotation IEA GO IEA HRH4 binds Hist HRH4 binds Hist This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 390899 1 Reactome DB_ID: 9800847 1 UniProt:Q91ZY2 Hrh4 UniProt Q91ZY2 1 EQUAL 390 EQUAL Reactome DB_ID: 9800849 1 HRH4:Hist [plasma membrane] HRH4:Hist Reactome DB_ID: 390899 1 Reactome DB_ID: 9800847 1 1 EQUAL 390 EQUAL Reactome Database ID Release 81 9800849 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9800849 Reactome R-MMU-390876 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-390876.1 Reactome Database ID Release 81 9802908 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9802908 Reactome R-MMU-390886 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-390886.1 Histamine H4 receptor (HRH4) (Nakamura et al. 2000) is highly expressed in bone marrow and white blood cells. It is also found in other tissues such as colon, liver, lungs and thymus. HRH4 mediates mast cell chemotaxis. Both the H3 and H4 receptors mediate their actions by coupling with the G protein alpha-i subtype, decreasing intracellular cAMP. 11118334 Pubmed 2000 Molecular cloning and characterization of a new human histamine receptor, HH4R Nakamura, T Itadani, H Hidaka, Y Ohta, M Tanaka, K Biochem Biophys Res Commun 279:615-20 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 81 9885086 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9885086 Reactome R-MMU-390650 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-390650.1 Histamine is a biogenic amine involved in local immune responses, regulation of gut function and neurotransmission. It exerts its actions by binding to histamine receptors. There are four receptors in humans, H1-H4 (Hill SJ et al, 1997). inferred by electronic annotation IEA GO IEA