ReviewDopamine receptors and brain function
Section snippets
The molecular biology of dopamine receptors: from D1 to D5
The introduction of gene cloning procedures to the neurotransmitter receptor field (for a review see Caron et al., 1990) resulted in a major shift in the understanding of the dopamine receptor system, and their previously unappreciated diversity was revealed. Bunzow et al. (1988)opened a new area in dopamine receptor research by cloning the first dopamine receptor cDNA, that of the D2 receptor. It was demonstrated that dopamine receptors belong to the large G protein-coupled receptor family.
Signal transduction of the dopamine receptors
The co-expression of various subtypes of dopamine receptors in the same brain region (such as the D1 and D2 in the striatum) and the inability to specifically target a dopamine receptor subtype by completely selective ligands makes it difficult to study the signal transduction associated with their activation in an intact tissue. The molecular cloning of the dopamine receptors has allowed the study of the properties of individual receptors in cultured cell lines. This has made it possible to
Distribution of the dopamine receptors in the central nervous system
Dopaminergic neurons are localized mainly in the substantia nigra pars compacta, the ventral tegmental area and the hypothalamus. They define three main pathways, the nigrostriatal, the mesolimbic and the tuberoinfundibular. Since selective radioligands capable of discriminating each member of the dopamine receptor family are unavailable, the study of dopamine receptor distribution in the brain by classic autoradiography binding techniques has been difficult. Thus, in situ hybridization has
Dopamine receptors and regulation of gene expression in the nigro-striatal pathway
The study of receptor and peptide levels in the striatum following perturbation of dopamine transmission is useful in better understanding the consequences of blockade of dopamine receptors (as occurring following neuroleptic treatment), interruption of dopaminergic transmission (as occurring in Parkinson's disease) or following the hyperactivation of the dopamine system (observed following abuse of psychostimulants such as cocaine and amphetamine).
Striatal efferent neurons are known to be
Dopamine receptors in the pituitary
The first direct evidence for the presence of dopamine receptors in the pituitary came from binding studies showing that high affinity, saturable and stereoselective binding sites for dopamine were detectable in the anterior (Creese et al., 1977; Caron et al., 1978; Bethea et al., 1982) and intermediate (Munemura et al., 1980; Lightman et al., 1982; Kohler and Fahlberg, 1985) lobes of the gland. On the basis of biochemical and pharmacological criteria, pituitary dopamine receptors were
Dopamine receptors and schizophrenia
The hypothesis that the dopaminergic system is overactive in schizophrenia is based on the finding that neuroleptics, which are used in the successful management of some symptoms of this disorder, selectively block dopamine receptors (Matthysse, 1974; Seeman, 1980; Kane and Freeman, 1994; Sigmundson, 1994). The dopamine hypothesis was further strengthened by the fact that psychostimulants, such as amphetamine, that increase dopaminergic transmission mainly by increasing the release of dopamine,
Transgenic animals: new frontiers for studying dopaminergic neurotransmission
The ability to make genetic changes in a predetermined way has provided an invaluable new tool to study individual players of dopaminergic transmission. In our laboratory, we have produced transgenic animals that express β galactosidase under the control of the D1 promoter to study the pattern of expression of the D1 receptor gene in the central nervous system (Severynse et al., 1995). β Galactosidase expression in the brain was found to closely match that of the D1 receptor mRNA previously
Perspectives
The last 30 years of research on the dopamine system have produced a wealth of information about the structure, function and regulation of the dopamine receptors. However, many unanswered questions remain. These include the functional role of the newest members of the dopamine receptor family (D3, D4 and D5), the significance of splice variants of the D2-like receptors, the relevance of the allelic variants found in the D4 receptor and whether a specific dopamine receptor is involved in the
Acknowledgements
M.J. was a recipient of an EMBO long term fellowship. C.M. was on sabbatical leave from the University of Brescia, Italy. M.G.C. is the beneficiary of a Bristol-Myers Squibb Unrestricted Neuroscience Award. We would like to thank Drs C. Le Moine and B. Bloch for helpful comments.
References (189)
- et al.
D2 dopamine receptor localization on striatonigral neurons
Neurosci. Lett.
(1992) - et al.
Striatal neurons express increased level of dopamine D2 receptor mRNA in response to haloperidol treatment: a quantitative in situ hybridization study
Neuroscience
(1991) - et al.
Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA
Brain Res.
(1991) - et al.
Quantitative in situ hybridization evidence for differential regulation of proenkephalin and dopamine D2 receptor mRNA levels in the rat striatum: effects of unilateral intrastriatal injections of 6-hydroxydopamine
Molec. Brain Res.
(1992) - et al.
Dopaminergic receptors in the anterior pituitary gland
J. Biol. Chem.
(1978) - et al.
Morphine activation of c-fos expression in rat brain
Biochem. Biophys. Res. Commun.
(1988) - et al.
D4 dopamine receptor-mediated signaling events determined in transfected Chinese hamster ovary cells
J. Biol. Chem.
(1994) - et al.
Molecular biology of the dopamine receptors
Eur. J. Pharmacol.
(1991) - et al.
[3H]-Spiperone labels dopamine receptors in pituitary and brain
Eur. J. Pharmacol.
(1977) - et al.
The dopamine D1D receptor. Cloning and characterization of three pharmacologically distinct D1-like receptors from Gallus domesticus
J. Biol. Chem.
(1995)
Mechanisms of action of atypical antipsychotic drugs. Implications for novel therapeutic strategies for schizophrenia
Schizophrenia Res.
Phenotypical characterization of neurons expressing the dopamine D3 receptor in the rat brain
Neuroscience
Inhibitory control of prolactin and Pit-1 gene promoters by dopamine. Dual signaling pathways required for D2 receptor regulated expression of the prolactin gene
J. Biol. Chem.
Angiotensin II and dopamine modulate both cAMP and inositol phosphate production in anterior pituitary cells
J. Biol. Chem.
Dual mechanisms of inhibition by dopamine of basal and thyrotropin-releasing hormone-stimulated inositol phosphate production in anterior pituitary cells
J. Biol.Chem.
A novel short isoform of the D3 dopamine receptor generated by alternative splicing in the third cytoplasmic loop
J. Biol. Chem.
Dopaminergic inhibition of DNA synthesis in pituitary tumor cells is associated with phosphotyrosine phosphatase activity
J. Biol. Chem.
Multiple receptors coupled to adenylate cyclase regulate Na–H exchange independent of cAMP
J. Biol. Chem.
Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways
Brain Res.
Dopamine-inhibited adenylate cyclase in female rat adenohypophysis
Life Sci.
Molecular characterization of the dopamine transporter
Trends Pharmacol. Sci.
Shorter variants of the D3 dopamine receptor produced through various patterns of alternative splicing
Biochem. Biophys. Res. Commun.
A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype
Cell
Reserpine treatment stimulates enkephalin and D2 dopamine receptor gene expression in the rat striatum
Molec. Brain Res.
Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striatum and pituitary
Molec. Brain Res.
Effect of reserpine treatment on the preproenkephalin mRNA level in the rat striatum: an in situ hybridization study
Molec. Brain Res.
Acute and chronic amphetamine treatments differently regulate neuropeptide mRNA levels and Fos immunoreactivity in rat striatal neurons
Neuroscience
Coupling of human D-1 dopamine receptors to different guanine nucleotide binding proteins. Evidence that D-1 dopamine receptors can couple to both Gs and Go
J. Biol. Chem.
Expression of the D3 dopamine receptor in peptidergic neurons of the nucleus accumbens: comparison with the D1 and D2 dopamine receptors
Neuroscience
The adrenergic receptors: models for the study of receptors coupled to guanine nucleotide regulatory proteins
J. Biol. Chem.
Colocalization of D1 and D2 dopamine receptor messenger RNAs in striatal neurons
Brain Res.
A dopamine-responsive domain in the N-terminal sequence of Pit-1
J. Biol. Chem.
Localization of [3H]spiperone binding sites in the intermediate lobe of the rat pituitary gland
Neurosci. Lett.
G protein specificity in receptor–effector coupling. Analysis of the roles of Go and Gi2 in GH4C1 pituitary cells
J. Biol. Chem.
Dialysis of lactotropes with antisense oligonucleotides assigns guanine nucleotide binding protein subtypes to their channel effectors
Molec. Endocrinol.
Parkinsonian-like locomotor impairement in mice lacking dopamine D2 receptors
Nature
Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain
J. Neurosci.
Characterization of the dopaminergic regulation of human prolactin-secreting cells cultured on extracellular matrix
J. Clin. Endocrinol. Metab.
Expression of dopamine D2 receptor and choline acetyltransferase mRNA in the dopamine deafferented rat caudate-putamen
Exp. Brain Res.
Stimulation by dopamine of adenylate cyclase in retinal homogenates and of adenosine-3′:5′-cyclic monophosphate formation in intact retina
Proc. Natn. Acad. Sci. U.S.A.
Changes in dopamine D1, D2 and D3 receptor mRNA levels in the rat brain following antipsychotic treatment
Psychopharmacology
Cloning and expression of a rat D2 dopamine receptor cDNA
Nature
The inhibition of phosphatidylinositol turnover: a possible post receptor mechanism for the prolactin secretion-inhibiting effect of dopamine
Endocrinology
Treatment of negative symptoms
Schizophrenia Bull.
Transfected D2 short dopamine receptors inhibit voltage-dependent potassium current in neuroblastoma×glioma hybrid (NG108-15) cells
Molec. Pharmacol.
Potassium channels involved in the transduction mechanism of dopamine D-2 receptors in rat lactotrophs
J. Physiol. (Lond.)
Regulation of the pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds
Proc. Natn. Acad. Sci. U.S.A.
A second molecular form of D2 dopamine receptor in rat and bovine caudate nucleus
Nature
Cited by (463)
From dopamine 4 to sigma 1: Synthesis, SAR and biological characterization of a piperidine scaffold of σ1 modulators
2022, European Journal of Medicinal ChemistrySynthesis and characterization of graphene oxide- Cu NPs-Fe-MOF nanocomposite and its application to simultaneous determination of Eskazina and Dopamine in real samples
2022, Journal of Electroanalytical ChemistryCitation Excerpt :DA is synthesized through l-DOPA enzymatic reactions in the kidneys and brain. So that, its deficit in biological fluids can leads to various diseases and neurological disorders like the schizophrenia, tourette syndrome, bipolar disorder and parkinson disease [10]. Therefore, quantification of DA at low levels of concentration can be attractive to assay the mechanism of neurological disorders.
Anticancer efficacy of endo- and exogenous potent ligands acting at dopaminergic receptor-expressing cancer cells
2022, European Journal of PharmacologyCitation Excerpt :Both groups of DA receptor subtypes differ specifically in their effects on cyclic adenosine monophosphate cAMP production as well as in localization (Fig. 1, Table 1). The D1-like receptors activate Gαs/olf and stimulate cAMP production, whereas the D2-like receptors are known for their ability to activate Gαi/o to inhibit adenylate cyclase activity and further cAMP production (Jaber et al., 1996). Such differences in the type of G-protein coupling activity were found to be associated with a specific motif in the sixth element (6TM) of the seven-transmembrane (7TM) dopamine receptors.