Multiple dopamine D4 receptor variants in the human population.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print Cited Medium: Print ISSN: 0028-0836 (Print) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
    • Publication Information:
      Publication: Basingstoke : Nature Publishing Group
      Original Publication: London, Macmillan Journals ltd.
    • Subject Terms:
      Genetic Variation* ; Receptors, Dopamine D2*; Receptors, Dopamine/*genetics; Base Sequence ; Binding, Competitive ; Cell Line ; Clozapine/metabolism ; DNA/chemistry ; DNA/isolation & purification ; DNA Restriction Enzymes ; Gene Expression ; Humans ; Introns ; Molecular Sequence Data ; Pituitary Gland/chemistry ; Receptors, Dopamine/metabolism ; Receptors, Dopamine D4 ; Repetitive Sequences, Nucleic Acid ; Spiperone/metabolism ; Substantia Nigra/chemistry ; Transfection
    • Abstract:
      The dopamine D4 receptor structurally and pharmacologically resembles the dopamine D2 and D3 receptors. Clozapine, an atypical antipsychotic that is relatively free of the adverse effects of drug-induced parkinsonism and tardive dyskinesia, binds to the D4 receptor with an affinity 10 times higher than to the D2 and D3 receptors. This may explain clozapine's atypical properties. Here we report the existence of at least three polymorphic variations in the coding sequence of the human D4 receptor. A 48-base-pair sequence in the putative third cytoplasmic loop of this receptor exists either as a direct-repeat sequence (D4.2), as a fourfold repeat (D4.4) or as a sevenfold repeat (D4.7). Two more variant alleles were detected in humans. Expression of the complementary DNA for the three cloned receptor variants showed different properties for the long form (D4.7) and the shorter forms (D4.2, D4.4) with respect to clozapine and spiperone binding. To our knowledge, this is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population. Such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to antipsychotic medication.
    • Comments:
      Comment in: Nature. 1992 Dec 3;360(6403):424. (PMID: 1448166)
      Comment in: Nature. 1992 Jul 9;358(6382):109. (PMID: 1614543)
    • Molecular Sequence:
      GENBANK UNKNOWN
    • Accession Number:
      0 (DRD4 protein, human)
      0 (Receptors, Dopamine)
      0 (Receptors, Dopamine D2)
      137750-34-6 (Receptors, Dopamine D4)
      4X6E73CJ0Q (Spiperone)
      9007-49-2 (DNA)
      EC 3.1.21.- (DNA Restriction Enzymes)
      J60AR2IKIC (Clozapine)
    • Publication Date:
      Date Created: 19920709 Date Completed: 19920730 Latest Revision: 20220310
    • Publication Date:
      20221208
    • Accession Number:
      10.1038/358149a0
    • Accession Number:
      1319557