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Trends in Neurosciences Oct 1997Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the motor... (Review)
Review
Increasing evidence suggests that antagonistic interactions between specific subtypes of adenosine and dopamine receptors in the basal ganglia are involved in the motor depressant effects of adenosine receptor agonists and the motor stimulant effects of adenosine receptor antagonists, such as caffeine. The GABAergic striatopallidal neurons are regulated by interacting adenosine A2A and dopamine D2 receptors. On the other hand, the GABAergic striatonigral and striatoentopeduncular neurons seem to be regulated by interacting adenosine A1 and dopamine D1 receptors. Furthermore, behavioural studies have revealed interactions between adenosine A2A and dopamine D1 receptors that occur at the network level. These adenosine-dopamine receptor-receptor interactions might offer new therapeutic leads for basal ganglia disorders.
Topics: Animals; Basal Ganglia; Behavior; Behavior, Animal; Humans; Receptors, Dopamine; Receptors, Purinergic P1
PubMed: 9347617
DOI: 10.1016/s0166-2236(97)01096-5 -
Clinical Neuropharmacology Aug 1993The recently discovered dopamine D3 receptor can be considered as a D2-like receptor: it is encoded by a gene comprising several introns; it is both an autoreceptor and... (Review)
Review
The recently discovered dopamine D3 receptor can be considered as a D2-like receptor: it is encoded by a gene comprising several introns; it is both an autoreceptor and a postsynaptic receptor, well recognized by antipsychotics. It differs, however, from the D2 receptor by a much more discrete expression, mostly in few limbic brain areas, e.g. shell of nucleus accumbens, islands of Calleja, and a considerably higher affinity for dopamine. Two association studies preliminarily suggest that the homozygotes for a D3 receptor gene polymorphism display twofold higher risk of schizophrenia, whereas several linkage studies led to inconclusive results.
Topics: Amino Acid Sequence; Animals; Antipsychotic Agents; Humans; Molecular Sequence Data; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 8104095
DOI: 10.1097/00002826-199308000-00002 -
CNS Neuroscience & Therapeutics Feb 2011Over the past two decades the dopamine D2 receptor has been undoubtedly the most widely studied dopamine receptor for the therapeutic treatment of schizophrenia, as the... (Review)
Review
Over the past two decades the dopamine D2 receptor has been undoubtedly the most widely studied dopamine receptor for the therapeutic treatment of schizophrenia, as the majority of antipsychotics exhibit antagonism at this receptor. However, the cognitive symptoms of the disorder are mostly resistant to the majority of available antipsychotic treatments and, as a result, there is a critical need to develop novel therapies that ameliorate all symptoms. The recognition that dopamine receptors, such as all G protein-coupled receptors (GPCRs), exist as oligomeric complexes has provided new avenues for drug design in the search for novel therapies. Furthermore, that it is now known that dopamine receptors can form heteromers, such as the dopamine D1-D2 receptor heteromer, with pharmacology and function distinct from its constituent receptors, has significantly expanded the range of potential drug targets. The aim of this review is to discuss the therapeutic relevance of these dopamine receptor oligomers to schizophrenia and to address the potential value of dopamine receptor heteromers in the search for new therapeutic strategies.
Topics: Antipsychotic Agents; Dopamine Agents; Humans; Multiprotein Complexes; Polymers; Protein Conformation; Receptors, Dopamine D1; Receptors, Dopamine D2; Schizophrenia
PubMed: 21199449
DOI: 10.1111/j.1755-5949.2010.00228.x -
Pediatric Nephrology (Berlin, Germany) Dec 2008Dopamine is important in the pathogenesis of hypertension because of abnormalities in receptor-mediated regulation of renal sodium transport. Dopamine receptors are... (Review)
Review
Dopamine is important in the pathogenesis of hypertension because of abnormalities in receptor-mediated regulation of renal sodium transport. Dopamine receptors are classified into D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), D(4)) subtypes, all of which are expressed in the kidney. Mice deficient in specific dopamine receptors have been generated to provide holistic assessment on the varying physiological roles of each receptor subtype. This review examines recent studies on these mutant mouse models and evaluates the impact of individual dopamine receptor subtypes on blood pressure regulation.
Topics: Animals; Disease Models, Animal; Dopamine; Hypertension; Kidney; Mice; Mice, Knockout; Receptors, Dopamine; Receptors, G-Protein-Coupled; Sodium
PubMed: 18615257
DOI: 10.1007/s00467-008-0901-3 -
Neuroscience and Biobehavioral Reviews Jul 2001Behavioral sensitization is a progressive, enduring enhancement of behaviors that develops following repeated stimulant administration. It is mediated in part by... (Review)
Review
Behavioral sensitization is a progressive, enduring enhancement of behaviors that develops following repeated stimulant administration. It is mediated in part by dopaminergic pathways that also modulate a number of psychiatric conditions including the development of psychosis. We propose that down-regulation of D3 dopamine receptor function in critical brain regions contributes to sensitization. Rodent locomotion, a sensitizable behavior, is regulated by the opposing influence of dopamine receptor subtypes, with D3 stimulation opposing concurrent D1 and D2 receptor activation. The D3 dopamine receptor has a 70-fold greater affinity for dopamine than D1 or D2 dopamine receptors. This imbalance in ligand affinity dictates greater occupancy for D3 than D1 or D2 receptors at typical dopamine concentrations following stimulant drug administration, resulting in differences in the relative tolerance at D3 vs D1 and D2 receptors. Sensitization may therefore result in part from accommodation of the inhibitory D3 receptor 'brake' on D1/D2 mediated behaviors, leading to a progressive locomotion increase following repeated stimulant exposure. The requirement for differential tolerance at D3 vs D1 and D2 receptors may explain the observed development of sensitization following application of cocaine, but not amphetamine, directly into nucleus accumbens. If correct, the 'D3 Dopamine Receptor Hypothesis' suggests D3 antagonists could prevent sensitization, and may interrupt the development of psychosis when administered during the prodromal phase of psychotic illness. Additional study is needed to clarify the role of the D3 dopamine receptor in sensitization and psychosis.
Topics: Animals; Behavior; Behavior, Animal; Dopamine; Humans; Nervous System; Psychotic Disorders; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 11566480
DOI: 10.1016/s0149-7634(01)00023-9 -
Medicinski Pregled 1996Dopamine is a neurotransmitter in both central and peripheral nervous system. In the central nervous system dopamine is involved in regulation of: movements, emotional... (Review)
Review
Dopamine is a neurotransmitter in both central and peripheral nervous system. In the central nervous system dopamine is involved in regulation of: movements, emotional processing of sensory input, appetite, vomiting and secretion of anterior pituitary hormones. The most important peripheral effect of dopamine is control of splanchnic and renal blood flows. There are five subtypes of dopamine receptors. D1 receptors are responsible for majority of peripheral dopamine effects; in the brain they modulate activity of limbic system. Symptoms of schizophrenia are produced by increased activation of D2 and D4 receptors. On the other hand, Parkinson's syndrome could be induced by D2 receptors blockade. D3 receptors decrease craving in drug-dependent laboratory animals. Although D5 receptors were found in many brain regions and in peripheral blood lymphocytes, their functions remain unknown. Linking dopamine receptor subtypes with actual effects of dopamine will enable more selective therapy of disorders caused by malfunction of this important system.
Topics: Animals; Brain; Humans; Receptors, Dopamine
PubMed: 8926944
DOI: No ID Found -
Psychopharmacology Jan 1998The D3 dopamine receptor is a member of the family of D2-like dopamine receptors. Since the cloning and identification of the D3 receptor in 1990, considerable progress... (Review)
Review
The D3 dopamine receptor is a member of the family of D2-like dopamine receptors. Since the cloning and identification of the D3 receptor in 1990, considerable progress has been made towards understanding the function of this novel site. Although some avenues of investigation have yielded more definitive results than others, studies to date indicate the D3 receptor is localized preferentially in limbic brain areas and affects locomotion and perhaps reinforcement and reward. A subpopulation of the receptors appear to be autoreceptors which modulate dopamine synthesis, release, and neuronal activity. These observations have led to the hypothesis that the D3 receptor may be an appropriate target in the treatment of neuropsychiatric disorders such as schizophrenia and drug addiction. The role of D3 sites in disease, however, remains to be established. Genetic association of D3 receptor polymorphisms with neuropsychiatric disorders have been proposed. Alterations in expression of D3 sites may occur in some diseases. Although the study of this receptor is clearly in the early stages, these findings lay the foundation for future investigation. In this review, dopamine D3 receptor brain localization, cellular signaling mechanisms, and associated behavior will be discussed. The potential role of the D3 site in neuropsychiatric disorders and as a therapeutic target is also addressed.
Topics: Animals; Behavior, Animal; Brain; Dopamine Antagonists; Humans; Receptors, Dopamine D2; Receptors, Dopamine D3; Signal Transduction
PubMed: 9489928
DOI: 10.1007/s002130050479 -
International Journal of Molecular... May 2018Some dopamine receptor subtypes were reported to participate in autophagy regulation, but their exact functions and mechanisms are still unclear. Here we found that...
Some dopamine receptor subtypes were reported to participate in autophagy regulation, but their exact functions and mechanisms are still unclear. Here we found that dopamine receptors D2 and D3 (D2-like family) are positive regulators of autophagy, while dopamine receptors D1 and D5 (D1-like family) are negative regulators. Furthermore, dopamine and ammonia, the two reported endogenous ligands of dopamine receptors, both can induce dopamine receptor internalization and degradation. In addition, we found that AKT (protein kinase B)-mTOR (mechanistic target of rapamycin) and AMPK (AMP-activated protein kinase) pathways are involved in DRD3 (dopamine receptor D3) regulated autophagy. Moreover, autophagy machinery perturbation inhibited DRD3 degradation and increased DRD3 oligomer. Therefore, our study investigated the functions and mechanisms of dopamine receptors in autophagy regulation, which not only provides insights into better understanding of some dopamine receptor-related neurodegeneration diseases, but also sheds light on their potential treatment in combination with autophagy or mTOR pathway modulations.
Topics: AMP-Activated Protein Kinase Kinases; Ammonia; Autophagy; Dopamine Agents; HEK293 Cells; HeLa Cells; Humans; Protein Kinases; Proto-Oncogene Proteins c-akt; Receptors, Dopamine; TOR Serine-Threonine Kinases
PubMed: 29786666
DOI: 10.3390/ijms19051540 -
Neuropsychopharmacology : Official... Oct 2000Evidence has been obtained for adenosine/dopamine interactions in the central nervous system. There exists an anatomical basis for the existence of functional... (Review)
Review
Evidence has been obtained for adenosine/dopamine interactions in the central nervous system. There exists an anatomical basis for the existence of functional interactions between adenosine A(1)R and dopamine D(1)R and between adenosine A(2A) and dopamine D(2) receptors in the same neurons. Selective A(1)R agonists affect negatively the high affinity binding of D(1) receptors. Activation of A(2A) receptors leads to a decrease in receptor affinity for dopamine agonists acting on D(2) receptors, specially of the high-affinity state. These interactions have been reproduced in cell lines and found to be of functional significance. Adenosine/dopamine interactions at the behavioral level probably reflect those found at the level of dopamine receptor binding and transduction. All these findings suggest receptor subtype-specific interactions between adenosine and dopamine receptors that may be achieved by molecular interactions (e.g., receptor heterodimerization). At the molecular level adenosine receptors can serve as a model for homomeric and heteromeric protein-protein interactions. A1R forms homodimers in membranes and also form high-order molecular structures containing also heterotrimeric G-proteins and adenosine deaminase. The occurrence of clustering also clearly suggests that G-protein- coupled receptors form high-order molecular structures, in which multimers of the receptors and probably other interacting proteins form functional complexes. In view of the occurrence of homodimers of adenosine and of dopamine receptors it is speculated that heterodimers between these receptors belonging to two different families of G-protein-coupled receptors can be formed. Evidence that A1/D1 can form heterodimers in cotransfected cells and in primary cultures of neurons has in fact been obtained. In the central nervous system direct and indirect receptor-receptor interactions via adaptor proteins participate in neurotransmission and neuromodulation and, for example, in the establishment of high neural functions such as learning and memory.
Topics: Animals; Central Nervous System; Dimerization; GTP-Binding Proteins; Humans; Models, Biological; Receptors, Dopamine; Receptors, Purinergic P1; Signal Transduction
PubMed: 11008067
DOI: 10.1016/S0893-133X(00)00144-5 -
Clinical and Experimental Hypertension... 1997Radioligand binding assay techniques associated with light microscope autoradiography were used for investigating the pharmacological profile and the micro anatomical... (Review)
Review
Radioligand binding assay techniques associated with light microscope autoradiography were used for investigating the pharmacological profile and the micro anatomical localization of peripheral dopamine receptor subtypes. In systemic arteries, the predominant dopamine D1-like receptor belongs to the D5 (or D1B) subtype. It is located within smooth muscle of the tunica media. In pulmonary arteries, dopamine D1-like receptors have primarily an endothelial localization and belong to the dopamine D1 (or D1A) receptor subtype. Both systemic and pulmonary arteries express a dopamine D2-like receptor belonging to the D2 receptor subtype. It has a prejunctional localization in the majority of vascular beds investigated. In cerebral, coronary and mesenteric arteries, it has also an endothelial localization. In the heart, a dopamine D4 receptor was identified. It is expressed by atrial tissue and has a widespread distribution overall atrial musculature. The kidney expresses both dopamine D1-like and D2-like receptors. Renal dopamine D1-like receptors have a vascular and tubular localization. The majority of these sites belongs to the D5 receptor subtype. A smaller D1 receptor population has primarily a tubular localization. Renal dopamine D2-like receptors belong to the dopamine D3 subtype and in lesser amounts to the D2 and D4 receptor subtypes. Renal dopamine D3 receptor has to a greater extent a tubular localization, whereas the D4 receptor is located within glomerular arterioles. The above results suggest that radioligand binding assay and autoradiographic techniques, if performed in the presence of compounds displaying specific receptor subtype selectivity, may contribute to characterize, mainly from a quantitative point of view, peripheral dopamine receptors.
Topics: Animals; Autoradiography; Humans; Kidney; Muscle, Smooth, Vascular; Myocardium; Receptors, Dopamine; Sensitivity and Specificity
PubMed: 9028633
DOI: 10.3109/10641969709080802