Discovery of a novel member of the histamine receptor family Public Deposited

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  • Nguyen, Tuan
    • Other Affiliation: The Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  • George, Susan R.
    • Other Affiliation: The Centre for Addiction and Mental Health, Toronto, Ontario, Canada and Departments of Pharmacology and Medicine, University of Toronto, Toronto, Canada
  • O'Dowd, Brian F.
    • Other Affiliation: The Centre for Addiction and Mental Health, Toronto, Ontario, Canada and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
  • Cheng, Regina
    • Other Affiliation: The Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  • Lee, Dennis K.
    • Other Affiliation: Department of Pharmacology, University of Toronto, Toronto, Canada
  • Roth, Bryan L.
    • ORCID: https://orcid.org/0000-0002-0561-6527
    • Other Affiliation: Department of Biochemistry and National Institute of Mental Health Psychoactive Drug Screening Program, Case Western Reserve University Medical School, Cleveland, OH
  • Setola, Vincent
    • Other Affiliation: Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH
  • Shapiro, David A.
    • Other Affiliation: Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH
  • Lynch, Kevin R.
    • Other Affiliation: Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, VA
  • Rauser, Laura
    • Other Affiliation: National Institute of Mental Health Psychoactive Drug Screening Program, Case Western Reserve University Medical School, Cleveland, OH
  • Lee, Samuel P.
    • Other Affiliation: Department of Pharmacology, University of Toronto, Toronto, Canada
Abstract
  • We report the discovery, tissue distribution and pharmacological characterization of a novel receptor, which we have named H4. Like the three histamine receptors reported previously (H1, H2, and H3), the H4 receptor is a G protein-coupled receptor and is most closely related to the H3 receptor, sharing 58% identity in the transmembrane regions. The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18. These sequences were used to retrieve a partial cDNA clone and, in combination with genomic fragments, were used to determine the full-length open reading frame of 390 amino acids. Northern analysis revealed a 3.0-kb transcript in rat testis and intestine. Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [3H]histamine (K d = 44 nM) and [3H]pyrilamine (K d = 32 nM) and several psychoactive compounds (amitriptyline, chlorpromazine, cyproheptadine, mianserin) with moderate affinity (K i range of 33–750 nM). Additionally, histamine induced a rapid internalization of HA-tagged H4 receptors in transfected human embryonic kidney 293 cells.
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Molecular Pharmacology
Journal volume
  • 59
Journal issue
  • 3
Page start
  • 427
Page end
  • 433
Language
  • English
Version
  • Postprint
ISSN
  • 0026-895X
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