The dopamine D(4) receptor: one decade of research.
Dopamine is an important neurotransmitter involved in motor control, endocrine function, reward, cognition and emotion. Dopamine receptors belong to the superfamily of G protein-coupled receptors and play a crucial role in mediating the diverse effects of dopamine in the central nervous system (CNS). The dopaminergic system is implicated in disorders such as Parkinson's disease and addiction, and is the major target for antipsychotic medication in the treatment of schizophrenia. Molecular cloning studies a decade ago revealed the existence of five different dopamine receptor subtypes in mammalian species. While the presence of the abundantly expressed dopamine D(1) and D(2) receptors was predicted from biochemical and pharmacological work, the cloning of the less abundant dopamine D(3), D(4) and D(5) receptors was not anticipated. The identification of these novel dopamine receptor family members posed a challenge with respect to determining their precise physiological roles and identifying their potential as therapeutic targets for dopamine-related disorders. This review is focused on the accomplishments of one decade of research on the dopamine D(4) receptor. New insights into the biochemistry of the dopamine D(4) receptor include the discovery that this G protein-coupled receptor can directly interact with SH3 domains. At the physiological level, converging evidence from transgenic mouse work and human genetic studies suggests that this receptor has a role in exploratory behavior and as a genetic susceptibility factor for attention deficit hyperactivity disorder.
Oak
J N
JN
Laboratory of Molecular Neurobiology, Centre for Addiction and Mental Health, Clarke Div., 250 College street, M5T 1R8, Toronto, Ontario, Canada.
Oldenhof
J
J
Van Tol
H H
HH
D000595:Amino Acid Sequence; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D050638:Receptors, Dopamine D4
C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D004298:Dopamine