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The American Journal of Physiology Sep 1989Dopamine, like other neurotransmitters, exerts its biological effects by occupation of specific receptor subtypes. The dopamine receptors in the central nervous system... (Comparative Study)
Comparative Study Review
Dopamine, like other neurotransmitters, exerts its biological effects by occupation of specific receptor subtypes. The dopamine receptors in the central nervous system and certain endocrine organs are classified into the D1/D2 subtypes. Outside the central nervous system, the dopamine receptors are classified into the DA1/DA2 subtypes. The D1/D2 and DA1/DA2 receptor have marked similarities and some differences, the most notable of which is the lower affinity of the DA dopamine compared with the D dopamine receptor. DA1 receptor activation increases renal blood flow (RBF); stimulation of DA1 and DA2 receptors may also increase glomerular filtration rate (GFR). DA1 agonists inhibit fluid and electrolyte transport indirectly via hemodynamic mechanisms and directly by occupation of DA1 receptors in specific nephron segments. In the proximal tubule, DA1 agonists simulate adenylate cyclase and inhibit Na+-H+ antiport activity. They also increase phospholipase C and inhibit Na+-K+-ATPase activity (presumably as a consequence of protein kinase C activation). The latter effects may be facilitated by DA2 agonists. In cortical collecting ducts, dopamine antagonizes the effects of mineralocorticoids and the hydrosomotic effect of antidiuretic hormone. It has also been suggested that DA1 may also decrease sodium transport by influencing other hormones, such as atrial natriuretic peptide. Studies of dopamine in the young are complicated because of the propensity for dopamine to stimulate alpha-adrenoceptors. Dopamine alone may actually decrease RBF in the perinatal period. In some animals, the renal vasodilatory and natriuretic effects of dopamine increase with age. Renal tubular DA1-stimulated adenylate cyclase activity increases, whereas renal tubular DA1 receptors decrease with age. Renal DA2 receptor density is greater in the fetus; after birth renal DA2 receptors do not change. Endogenous dopamine may regulate sodium excretion in the young differently than in the adult. In the adult, sodium surfeit is associated with an increase in urinary dopamine; the opposite occurs in the young. A decrease in dopamine production or blockade of dopamine receptors results in an antinatriuresis in the adult; dopamine blockade in the young results in a natriuresis. It remains to be determined whether these age-related differences in dopamine effects are due to changes in receptor DA subtype density, second messengers, and/or interaction with other receptors.
Topics: Animals; Biological Transport; Body Water; Dopamine; Dopamine Agents; Dopamine Antagonists; Kidney; Natriuresis; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Second Messenger Systems; Sodium; Tissue Distribution
PubMed: 2571302
DOI: 10.1152/ajprenal.1989.257.3.F315 -
Reviews in the Neurosciences 2007It is well established that learning and memory are complex processes involving and recruiting different brain modulatory neurotransmitter systems. Considerable evidence... (Review)
Review
It is well established that learning and memory are complex processes involving and recruiting different brain modulatory neurotransmitter systems. Considerable evidence points to the involvement of dopamine in various aspects of cognition, and interest has been focused on investigating the clinical relevance of dopamine systems to age-related cognitive decline and manifestations of cognitive impairment in schizophrenia, Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases. In the past decade or so, in spite of the molecular cloning of the five dopamine receptor subtypes, their specific roles in brain function remained inconclusive due to the lack of completely selective ligands that could distinguish between the members of the D1-like and D2-like dopamine receptor families. One of the most important advances in the field of dopamine research has been the generation of mutant mouse models permitting evaluation of the dopaminergic system using gene targeting technologies. These mouse models represent an important approach to explore the functional roles of closely related receptor subtypes. In this review, we present and discuss evidence on the role of dopamine receptors in different aspects of learning and memory at the cellular, molecular and behavioral levels. We compare evidence using conventional pharmacological, lesion or electrophysiological studies with results from mice with targeted deletions of different subtypes of dopamine receptor genes. We particularly focus on dopamine D1 and D2 receptors in an effort to delineate their specific roles in various aspects of cognitive function. We provide strong evidence, from our own recent work as well as others, that dopamine is part of the network that plays a very important role in cognitive function, and that although multiple dopamine receptor subtypes contribute to different aspects of learning and memory, the D1 receptor seems to play a more prominent role in mediating plasticity and specific aspects of cognitive function, including spatial learning and memory processes, reversal learning, extinction learning, and incentive learning.
Topics: Animals; Central Nervous System; Humans; Learning; Receptors, Dopamine; Signal Transduction
PubMed: 17405450
DOI: 10.1515/revneuro.2007.18.1.37 -
European Journal of Pharmacology Sep 2000Dopamine is an important neurotransmitter involved in motor control, endocrine function, reward, cognition and emotion. Dopamine receptors belong to the superfamily of G... (Review)
Review
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.
Topics: Amino Acid Sequence; Animals; Dopamine; Humans; Molecular Sequence Data; Receptors, Dopamine D2; Receptors, Dopamine D4
PubMed: 11033337
DOI: 10.1016/s0014-2999(00)00562-8 -
Wiener Klinische Wochenschrift 1991The classification of dopamine receptors and their neuroanatomical distribution is reviewed, including the newly discovered D3, D4 and D5 subtypes. In vivo imaging... (Review)
Review
The classification of dopamine receptors and their neuroanatomical distribution is reviewed, including the newly discovered D3, D4 and D5 subtypes. In vivo imaging techniques and methods for quantification are briefly described and PET and SPECT studies of D2 receptors in schizophrenia, under neuroleptic treatment, in aging, Parkinson's disease, Huntington's disease, tardive dyskinesia and multisystem atrophies are reviewed and compared with our own results. A short description is given of imaging studies of D1 receptors.
Topics: Brain; Brain Diseases; Dopamine; Humans; Neurocognitive Disorders; Radioligand Assay; Receptors, Dopamine; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon
PubMed: 1771898
DOI: No ID Found -
EXS 1994Our knowledge of dopamine receptor diversity has markedly increased during the past few years as a result of discovery of five distinct genes, splice variants and... (Review)
Review
Our knowledge of dopamine receptor diversity has markedly increased during the past few years as a result of discovery of five distinct genes, splice variants and polymorphic receptors. The genes can be classified in two subfamilies: the intronless genes that encode the D1 and D5 receptors positively linked to adenylyl cyclase and genes with introns that encode the two isoforms of the D2 receptor and the D3 and D4 receptors. The various dopamine receptor subtypes can be distinguished by their sequence, intracellular signalling systems, pharmacology and localisation. The localisation of the D3 receptor in the shell of nucleus accumbens suggests its participation in brain reward circuits and actions of substances of abuse.
Topics: Animals; Brain; Corpus Striatum; Humans; Multigene Family; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D3; Substance-Related Disorders
PubMed: 8032175
DOI: 10.1007/978-3-0348-7330-7_9 -
Hypertension Research : Official... Jun 1995Combined radioligand binding and light microscope autoradiography techniques were used for investigating the pharmacological profile and the microanatomical localisation... (Review)
Review
Combined radioligand binding and light microscope autoradiography techniques were used for investigating the pharmacological profile and the microanatomical localisation of dopamine receptor subtypes in the cardiovascular system and in the kidney. In superior mesenteric and renal arteries the predominant dopamine D1-like receptor belongs to the D5 (or D1b) subtype. This site is located within smooth muscle of the tunica media. The same receptor subtype predominates in the kidney, where it has a vascular and tubular localisation. The dopamine D2-like receptor subtype expressed by systemic arteries belongs to the D2 receptor subtype. It has a prejunctional and endothelial localisation. In the kidney the predominating dopamine D2-like receptor belongs to the dopamine D3 subtype. Atria but not ventricles express dopamine D2-like receptors belonging to the D4 receptor subtype. The above results suggest that in spite of the emerging complexity of the dopamine receptor profile demonstrated by molecular biology techniques, radioligand binding and autoradiographic techniques, if performed with appropriate radioligands and/or in the presence of compounds active on specific receptor subtypes, may represent a useful tool for better understanding the biological significance of peripheral dopamine receptors.
Topics: Animals; Cardiovascular System; Humans; Kidney; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 8529069
DOI: 10.1291/hypres.18.supplementi_s23 -
Neuropsychopharmacology : Official... Dec 1992Dopamine (DA) D2, D3, and D4 receptors are targets for antipsychotic drugs. The recent cloning, deoxyribonucleic acid sequencing, and brain location of these receptors... (Review)
Review
Dopamine (DA) D2, D3, and D4 receptors are targets for antipsychotic drugs. The recent cloning, deoxyribonucleic acid sequencing, and brain location of these receptors provide new insight on the DA hypothesis of schizophrenia, particularly for the basis of antipsychotic therapy of schizophrenia. In schizophrenia brain tissue, D2 receptors are elevated and have lost the link to D1 receptors. Brain positron-emission tomography studies of patients may also reveal elevated D2, depending on the method used. Hallucinations and positive symptoms are blocked when about 70% of the D2 receptors are occupied by neuroleptic drugs. An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs (in the patient's cerebrospinal fluid or plasma water) act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.
Topics: Amino Acid Sequence; Animals; Antipsychotic Agents; Clozapine; Humans; Molecular Sequence Data; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Dopamine D4
PubMed: 1362057
DOI: No ID Found -
Trends in Neurosciences Jun 1992Since the discovery that L-DOPA could alleviate the symptoms of Parkinson's disease, it has been assumed that the striatum is the site of action of the dopamine formed... (Review)
Review
Since the discovery that L-DOPA could alleviate the symptoms of Parkinson's disease, it has been assumed that the striatum is the site of action of the dopamine formed from L-DOPA. However, for the past 15 years, evidence has accumulated to suggest that dopamine is also released by the dendrites of dopamine neurons in the substantia nigra and D1 dopamine receptors in this region of the brain appear to play an important role in the actions of L-DOPA. Activation of D1 receptors in the substantia nigra may, in part, explain some of the synergistic effects of D1 and D2 agonists in animal models for Parkinson's disease. These effects are discussed in light of recent studies suggesting that dopamine, acting on D1 and D2 dopamine receptor subtypes, activates distinct efferent pathways from the striatum. Clinical studies suggest that these findings may have important implications for the treatment of Parkinson's disease.
Topics: Animals; Humans; Parkinson Disease; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 1378662
DOI: 10.1016/0166-2236(92)90034-6 -
General Pharmacology 19821. The clinical and experimental pharmacology of sulpiride, its effects on the CNS, gastrointestinal tract and cardiovascular system have been reviewed. 2. The majority... (Review)
Review
1. The clinical and experimental pharmacology of sulpiride, its effects on the CNS, gastrointestinal tract and cardiovascular system have been reviewed. 2. The majority of its actions are attributable to blockade of dopamine receptors. 3. Although sulpiride has a high affinity for dopamine receptors involved in emesis and prolactin secretion, it lacks part of the behavioural and biochemical profiles of the classical dopamine receptor antagonist neuroleptics. 4. In the cardiovascular system, sulpiride is a potent prejunctional dopamine receptor antagonist but has variable effectiveness in postjunctional dopamine receptor models. 5. These properties are discussed with reference to the mechanisms of action of sulpiride and the classification of dopamine receptors.
Topics: Animals; Cardiovascular System; Central Nervous System; Digestive System; Dopamine Antagonists; Humans; Prolactin; Receptors, Dopamine; Sulpiride
PubMed: 7047291
DOI: 10.1016/0306-3623(82)90088-x -
American Journal of Hypertension Apr 1996Dopamine produced by renal proximal tubules acts as an intrarenal natriuretic factor by direct tubular action; this paracrine effect is influenced by the state of sodium... (Review)
Review
Dopamine produced by renal proximal tubules acts as an intrarenal natriuretic factor by direct tubular action; this paracrine effect is influenced by the state of sodium balance. Up to 60% of sodium excretion with volume (2%-10%) expansion may be mediated by D1-like receptors. The renal paracrine effect of dopamine is impaired in genetic hypertension; this is due to defects in renal dopamine production or transduction of the dopamine signal. The Dahl salt sensitive rat and the spontaneously hypertensive rat (SHR), which have normal renal dopamine production and expression of dopamine receptors, have a defect in the coupling of a D1-like receptor to G-protein/effector enzyme complex. A consequence of the defective D1-like receptor/effector enzyme coupling in SHR is a decreased ability of D1 agonists to inhibit Na+/H+ exchange and Na+/K+-ATPase activity. The defect is 1) genetic, since it precedes the onset of and cosegregates with the hypertension; 2) receptor specific, since it is not shared by other humoral agents; and 3) confined to the renal proximal tubule. Two of the cloned dopamine receptors in mammals are D1-like (D1A and D1B). The D1A receptor gene is expressed to a greater extent in renal proximal tubules than the D1B receptor gene. The D1-like receptor is important in the pathogenesis of hypertension. Chronic blockade of dopamine receptors accelerates the development of hypertension in normotensive and hypertensive rats. Moreover, disruption of the D1A receptor gene in mice increases systolic blood pressure and results in diastolic hypertension. The abnormal D1-like receptor in SHR may be the D1A receptor; its uncoupling from the G-protein/effector enzyme complex in renal proximal tubules of SHR may be due to mistargeting. The mechanism for this "mistargeting" of the D1A receptor is not due to a mutation in the primary sequence and remains to be determined.
Topics: Animals; Dopamine; Humans; Hypertension; Kidney; Natriuresis; Rats; Rats, Inbred SHR; Receptors, Dopamine; Signal Transduction
PubMed: 8722444
DOI: 10.1016/0895-7061(95)00351-7