Expression and characterization of a dopamine D4R variant associated with delusional disorder.
Multiple genetic polymorphisms of the human dopamine D4 receptor (hD4R) have been identified including a 12 bp repeat in exon 1 associated with a psychotic condition called delusional disorder. Competition binding assays revealed minor pharmacological differences between the recombinant A1 (normal) and A2 (delusional) proteins with respect to quinpirole and the antipsychotic clozapine, however no functional differences were detected for receptor activation by dopamine, epinephrine, or norepinephrine. Our results suggest that this polymorphism may only confer susceptibility to delusional disorder in combination with other genetic or environmental factors.
Zenner
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MT
Hoffmann-La Roche, Pharmaceutical Research, Preclinical Neuroscience, Basel, Switzerland.
Nobile
M
M
Henningsen
R
R
Smeraldi
E
E
Civelli
O
O
Hartman
D S
DS
Catalano
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D016466:CHO Cells; D003024:Clozapine / Q000494:pharmacology; D006224:Cricetinae; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D014644:Genetic Variation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D011110:Polymorphism, Genetic; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D050638:Receptors, Dopamine D4; D011994:Recombinant Proteins / Q000378:metabolism; D012563:Schizophrenia, Paranoid / Q000235:genetics*; D014162:Transfection
D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D011994:Recombinant Proteins; D050638:Receptors, Dopamine D4; D019257:Quinpirole; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D003024:Clozapine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine