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Arzneimittel-Forschung Feb 1992A novel dopamine receptor has been recently cloned, which differs from D1 and D2 receptors by its sequence, localization, pharmacology and possibly signalling system,... (Review)
Review
A novel dopamine receptor has been recently cloned, which differs from D1 and D2 receptors by its sequence, localization, pharmacology and possibly signalling system, hence its designation as D3 receptor. The D3 receptor cDNA was obtained by a combination of screenings of DNA libraries and PCR polymerase chain reaction experiments. It encodes a protein with a predicted structure consisting in 7 transmembrane domains indicating that it belongs to the G-protein coupled receptor family. Its global homology is 52% with the D2 receptor but 78% if only transmembrane domains are considered. Two shorter transcript variants, in addition to the full-length cDNA were detected by PCR in various rat brain regions. The shorter transcripts are generated by alternative splicing and encode two putative proteins respectively interrupted after the second transmembrane domain and lacking the second extracytoplasmic loop. After transfection of this latter isoform into cultured cells, no dopaminergic activity could be detected. These shorter splice variants may regulate the number of active D3 receptors. The human D3 receptor was also cloned using similar approaches with rat D3 receptor cDNA probes and was found highly homologous to the rat receptor, except in the third intracytoplasmic loop. The human D3 receptor gene was assigned to the chromosome 3 at q13.3 band. Visualisation of D3 receptor mRNA in rat brain by in situ hybridization indicated a predominant expression of the message in the ventral striatum and other "limbic" areas. There is no overlap in the distributions of D2 and D3 receptor mRNAs in discrete structures, suggesting that the two transcripts are expressed by different cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Amino Acid Sequence; Animals; Brain; Brain Chemistry; Humans; Mental Disorders; Molecular Sequence Data; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 1586393
DOI: No ID Found -
The Canadian Journal of Neurological... Feb 1984The neuroleptic/dopamine receptor, with its picomolar affinity for potent neuroleptics, is the functional dopamine receptor of the brain. This receptor has been termed...
The neuroleptic/dopamine receptor, with its picomolar affinity for potent neuroleptics, is the functional dopamine receptor of the brain. This receptor has been termed the D2 dopamine receptor, and it inhibits or interferes with dopamine-stimulated adenylate cyclase. This D2 receptor has two states, each having different affinity for dopamine. The high-affinity state, termed D2 high, has a 10 nM affinity for dopamine and is the functional correlate for dopamine autoreceptors and for the dopamine receptor in the pituitary gland. The low-affinity state, termed D2 low, has a 2000 nM affinity for dopamine, and may possibly represent the desensitized state of the dopamine receptor or the functional post-synaptic receptor.
Topics: Animals; Binding Sites; Rats; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Synapses; Terminology as Topic
PubMed: 6231978
DOI: 10.1017/s0317167100046242 -
Advances in Experimental Medicine and... 1988The D-1 receptor will provide a fruitful ground for many scientists in the coming years. Pure biochemists will attempt to isolate, purify and sequence the molecule... (Review)
Review
The D-1 receptor will provide a fruitful ground for many scientists in the coming years. Pure biochemists will attempt to isolate, purify and sequence the molecule itself. Functional biochemists will study the mechanisms whereby the receptor regulates adenylate cyclase activity. Physiologists will attempt to study the consequences of stimulating the receptor in either the brain or in peripheral tissues. Animal behavioralists will attempt to understand how the receptor participates in the generation of animals response to dopaminergic drugs (both agonists and antagonists). Finally, it remains to be determined if any novel therapeutic agents targeted towards the D-1 receptor will become commercially viable compounds.
Topics: Adenylyl Cyclases; Animals; Brain; Parathyroid Glands; Receptors, Dopamine; Receptors, Dopamine D1; Retina
PubMed: 2976251
DOI: 10.1007/978-1-4899-2723-1_2 -
British Journal of Pharmacology Jan 2015The variety of physiological functions controlled by dopamine in the brain and periphery is mediated by the D1, D2, D3, D4 and D5 dopamine GPCRs. Drugs acting on... (Review)
Review
The variety of physiological functions controlled by dopamine in the brain and periphery is mediated by the D1, D2, D3, D4 and D5 dopamine GPCRs. Drugs acting on dopamine receptors are significant tools for the management of several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression and Parkinson's disease. Recent investigations of dopamine receptor signalling have shown that dopamine receptors, apart from their canonical action on cAMP-mediated signalling, can regulate a myriad of cellular responses to fine-tune the expression of dopamine-associated behaviours and functions. Such signalling mechanisms may involve alternate G protein coupling or non-G protein mechanisms involving ion channels, receptor tyrosine kinases or proteins such as β-arrestins that are classically involved in GPCR desensitization. Another level of complexity is the growing appreciation of the physiological roles played by dopamine receptor heteromers. Applications of new in vivo techniques have significantly furthered the understanding of the physiological functions played by dopamine receptors. Here we provide an update of the current knowledge regarding the complex biology, signalling, physiology and pharmacology of dopamine receptors.
Topics: Animals; Humans; Protein Multimerization; Receptors, Dopamine; Signal Transduction
PubMed: 25671228
DOI: 10.1111/bph.12906 -
Journal of the American Society of... Feb 1992Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and... (Review)
Review
Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and ion fluxes. Dopamine receptors in the brain have been classically divided into D1 and D2 subtypes, based on pharmacological data. However, molecular biology techniques have identified many more dopamine receptor subtypes. Several of the receptors cloned from the brain correspond to the classically described D1 and D2 receptors. Several D1 receptor subtypes have been cloned (D1A, D1B, and D5) and are each coupled to the stimulation of adenylyl cyclase. The D2 receptor has two isoforms, a shorter form, composed of 415 amino acids, is termed the D2short receptor. The long form, called the D2long receptor, is composed of 444 amino acids; both are coupled to the inhibition of adenylyl cyclase. The D3 and D4 receptors are closely related to, but clearly distinct from, the D2 receptor. They have not yet been linked to adenylyl cyclase activity. Outside of the central nervous system, the peripheral dopamine receptors have been classified into the DA1 and DA2 subtypes, on the basis of synaptic localization. The pharmacological properties of DA1 receptors roughly approximate those of D1 and D5 receptors, whereas those of DA2 receptors approximate those of D2 receptors. A renal dopamine receptor with some pharmacological features of the D2 receptor but not linked to adenylyl cyclase has been described in the renal cortex and inner medulla. In the inner medulla, this D2-like receptor, termed DA2k, is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2. Of the cloned dopamine receptors, only the mRNA of the D3 receptor has been reported in the kidney. The DA1 receptor in the kidney is associated with renal vasodilation and an increase in electrolyte excretion. The DA1-related vasodilation and inhibition of electrolyte transport is mediated by cAMP. The role of renal DA2 receptors remains to be clarified. Although DA1 and DA2 receptors may act in concert to decrease transport in the renal proximal convoluted tubule, the overall function of DA2 receptors may be actually the opposite of those noted for DA1 receptors. Dopamine has been postulated to act as an intrarenal natriuretic hormone. Moreover, an aberrant renal dopaminergic system may play a role in the pathogenesis of some forms of hypertension. A decreased renal production of dopamine and/or a defective transduction of the dopamine signal is/are present in some animal models of experimental hypertension as well as in some forms of human essential hypertension.
Topics: Humans; Hypertension, Renovascular; Kidney; Natriuresis; Receptors, Dopamine; Signal Transduction
PubMed: 1627751
DOI: 10.1681/ASN.V281265 -
Synapse (New York, N.Y.) 1987The present review focuses on the hypothesized D1/D2 dopamine (DA) receptor classification, originally based on the form of receptor coupling to adenylate cyclase... (Review)
Review
The present review focuses on the hypothesized D1/D2 dopamine (DA) receptor classification, originally based on the form of receptor coupling to adenylate cyclase activity. The pharmacological effects of compounds exhibiting putative selective agonist or antagonist profiles at those DA receptors positively coupled to adenylate cyclase activity (D1 DA receptors) are extensively reviewed. Comparisons are made with the effects of putative selective D2 DA receptor agonists and antagonists, and on the basis of this work, the DA receptor classification is critically evaluated. A variety of biochemical, behavioral, and electrophysiological evidence is presented which supports the view that D1 and D2 DA receptors can interact in both an opposing and synergistic fashion. Particular attention is focused on the possibility that D1 receptor stimulation is required to enable the expression of certain D2 receptor-mediated effects, and the functional consequences of this form of interaction are considered. A hypothetical model is presented which considers how both the opposing and enabling forms of interaction between D1 and D2 DA receptors can control behavioral expression. Finally, the clinical relevance of this work is discussed and the potential use of selective D1 receptor agonists and antagonists in the treatment of psychotic states and Parkinson's disease is considered.
Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Adenylyl Cyclases; Animals; Benzazepines; Brain; Humans; Rats; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Stereotyped Behavior
PubMed: 2971273
DOI: 10.1002/syn.890010408 -
Heart and Vessels Sep 2010The present study first time detected D1-D5 dopamine receptor subtypes in the native human heart simultaneously, found presence of D1, D2, D4, and D5 in cardiac tissues,...
The present study first time detected D1-D5 dopamine receptor subtypes in the native human heart simultaneously, found presence of D1, D2, D4, and D5 in cardiac tissues, and revealed distribution features of dopamine receptor subtypes in the epicardium, myocardium, and endocardium. Samples from four native hearts coming from young brain-dead donors, which for technical reason were not used for transplants, were studied. Dopamine receptors were revealed by immunochemistry technique and immunoblot analysis. Morphometrical quantification of the density of each receptor subtype was performed by an image analyzer. Our results demonstrate that only four subtypes of dopamine receptors can be found in cardiac tissues: D1, D2, D4, and D5. These dopamine receptors have been detected in endocardium, myocardium, and epicardium. D1 receptors were stored primarily in the epicardial layer. Dopamine receptors are distributed in the wall of both atria and ventricles, and its transmural gradient can be described in the wall of the human heart. Sections of atria and ventricles exposed to antidopamine receptor antibodies showed fluorescent-positive reaction in the epicardium, myocardium and endocardium. D4 receptor immune reactivity was remarkably less intense than D2 receptor immune reactivity. All the subtypes of dopamine receptors are in close relationships with all cardiac structures. Our findings provide a favorable basis for researching the role of dopamine receptors in controlling functions of the human heart and in the pathogenesis of cardiovascular diseases.
Topics: Adult; Blotting, Western; Endocardium; Humans; Immunohistochemistry; Myocardium; Pericardium; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D4; Receptors, Dopamine D5
PubMed: 20676967
DOI: 10.1007/s00380-009-1224-4 -
Journal of Autonomic Pharmacology 20001. Earlier studies have demonstrated a high density of dopamine D1-like receptor binding in the choroid plexus by light microscope autoradiography, but the dopaminergic...
1. Earlier studies have demonstrated a high density of dopamine D1-like receptor binding in the choroid plexus by light microscope autoradiography, but the dopaminergic specificity of this binding was questioned. 2. In this study the localization of dopamine receptor subtypes was investigated in the rat choroid plexus by Western blot analysis and immunohistochemistry using antibodies raised against dopamine D1-D5 receptor protein. 3. Western blot analysis revealed reactivity with immune bands of approximately 50 and 51 KDa corresponding to dopamine D1 and D5 receptors, respectively. Dopamine D1-like (D1 and D5) receptor protein immunoreactivity insensitive to superior cervical ganglionectomy was located in smooth muscle of choroid arteries and to a larger extent within choroid plexus epithelium. 4. Western blot analysis revealed reactivity with immune bands of approximately 53 KDa and 40-42 KDa corresponding to dopamine D2 and D4 receptors, respectively, and no dopamine D3 receptor reactivity. Dopamine D2-like receptor protein immunoreactivity displayed a distribution similar to that of tyrosine-hydroxylase (TH)-immunoreactive sympathetic fibres and disappeared after superior cervical ganglionectomy. It consisted in the expression of dopamine D2 and to a lesser extent of D4 receptor protein immunoreactivity perivascularly and associated with choroid epithelium. No D3 receptor protein immunoreactivity was found in rat choroid plexus. 5. The above results indicate that rat choroid plexus expresses dopamine receptor protein, being dopamine D1-like receptors predominant in epithelium and arterial smooth muscle and D2-like receptors in sympathetic nerve fibres supplying choroid plexus epithelium and vasculature. 6. These findings suggests that dopamine receptors with a different anatomical localization may modulate production of cerebrospinal fluid.
Topics: Animals; Blotting, Western; Choroid Plexus; Immunohistochemistry; Male; Molecular Weight; Rats; Rats, Wistar; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Receptors, Dopamine D5
PubMed: 11350498
DOI: 10.1046/j.1365-2680.2000.00198.x -
Psychopharmacology Series 1993
Review
Topics: Amino Acid Sequence; Animals; Brain Chemistry; Dopamine Agents; Humans; Kinetics; Molecular Sequence Data; Polymorphism, Genetic; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 8103228
DOI: 10.1007/978-3-642-78010-3_8 -
Journal of Receptor and Signal... Feb 2011Dopamine D(1)-D(5) receptors subtypes were studied in human coronary vessels of healthy subjects to assess their localization and their expression.
OBJECTIVE
Dopamine D(1)-D(5) receptors subtypes were studied in human coronary vessels of healthy subjects to assess their localization and their expression.
METHODS
Samples of intraparenchymal and extraparenchymal branches of human coronary arteries and veins were harvested from four normal native hearts explanted from four young brain dead heart donors in case of orthoptic transplant, not carried out for technical reasons. In all the samples morphological, biochemical, immunochemical, and morphometrical studies were performed including quantitative analysis of images and evaluation of data.
RESULTS
Microanatomical section showed healthy coronary vessels, which expressed all dopamine receptors (from D(1) to D(5)) with a different pattern of distribution between the different layers, in the intra and in the extraparenchymal branches.D(1) and D(5) (with a prevalence D(1) over D(5)) were distributed in the adventitia and to a lesser extent in the outer media but they were absent in arterioles, capillaries and venules. Endothelial and the middle layer showed D(2), D(3) and D(4) receptors, with a greater expression of D(2). Immunoblot analysis of dopamine monoclonal antibodies and dopamine receptors showed a different migration band for each receptor: D(1) (45 KDa); D(2) (43 KDa); D(3) (42 kDa); D(4) (40-42 KDa); D(5) (38-40 KDa)
CONCLUSION
These findings demonstrate the presence of all dopamine receptor subtypes in the wall of human coronary vessels of healthy subjects. Dopamine D(1) and D(2) receptor subtypes are the most expressed, suggesting their prominent role in the coronary vasoactivity.
Topics: Adult; Coronary Vessels; Densitometry; Endothelium, Vascular; Health; Humans; Immunoblotting; Receptors, Dopamine
PubMed: 20704467
DOI: 10.3109/10799893.2010.506878