scholarly journals The renal dopamine receptors.

1992 ◽  
Vol 2 (8) ◽  
pp. 1265-1278
Author(s):  
P A Jose ◽  
J R Raymond ◽  
M D Bates ◽  
A Aperia ◽  
R A Felder ◽  
...  
Keyword(s):  
Amino Acids ◽  
Adenylyl Cyclase ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
D2 Receptor ◽  
D2 Receptors ◽  
Receptor Subtypes ◽  
Renal Dopamine ◽  
The Brain ◽  
Stimulation Of

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.

Renal Dopamine Receptors and Hypertension

2003 ◽  
Vol 228 (2) ◽  
pp. 134-142 ◽  
Author(s):  
Tahir Hussain ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Proximal Tubule ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Sodium Excretion ◽  
Molecular Mechanisms ◽  
Sympathetic Ganglia ◽  
Receptor Subtypes ◽  
Receptor Function ◽  
The Central Nervous System ◽  
Renal Dopamine

Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which Include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D1 receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D1 receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.

Dopamine Receptors and Antipsychotic Drug Response

1993 ◽  
Vol 163 (S22) ◽  
pp. 31-38 ◽  
Author(s):  
Roger K. Sunahara ◽  
Philip Seeman ◽  
Hubert H. M. Van Tol ◽  
Hyman B. Niznik
Keyword(s):  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Antipsychotic Drug ◽  
Drug Response ◽  
Chromosomal Location ◽  
Receptor Subtypes ◽  
Receptor System ◽  
Dopamine Receptor Genes ◽  
The Brain ◽  
Receptor Family

Dopamine receptors have been divided into two major types – D1 and D2 – based primarily on pharmacological and biochemical criteria. Recent advances in the molecular biology of the dopamine receptor system have allowed the identification and characterisation of at least five distinct neuronal dopamine receptor genes (D1 to D5). These genes encode dopamine receptors belonging to the D1 receptor family, termed D1 and D5, and three D2-like receptors, termed D2, D3 and D4. These receptors are distinguished on the basis of their primary structure, chromosomal location, mRNA size and tissue distribution, and biochemical and pharmacological differences. Although individually these receptor subtypes may not be directly and exclusively involved in the maintenance or expression of schizophrenia, alterations of any of the receptors may contribute to the perturbation or instability of dopaminergic homeostasis in the brain. What was once thought to be a simple two-receptor system seems to have emerged as an intricate and interactive entity. This review summarises what is currently understood about dopamine receptors, their role in antipsychotic drug action, and their association with psychosis.

scholarly journals Classification of Dopamine Receptor Genes in Vertebrates: Nine Subtypes in Osteichthyes

2015 ◽  
Vol 86 (3-4) ◽  
pp. 164-175 ◽  
Author(s):  
Kei Yamamoto ◽  
Romain Fontaine ◽  
Catherine Pasqualini ◽  
Philippe Vernier
Keyword(s):  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Animal Studies ◽  
Phylogenetic Analyses ◽  
D2 Receptor ◽  
Receptor Subtypes ◽  
Brain Functions ◽  
History Of ◽  
Dopamine Receptor Genes ◽  
G Protein Coupled

Dopamine neurotransmission regulates various brain functions, and its regulatory roles are mediated by two families of G protein-coupled receptors: the D1 and D2 receptor families. In mammals, the D1 family comprises two receptor subtypes (D1 and D5), while the D2 family comprises three receptor subtypes (D2, D3 and D4). Phylogenetic analyses of dopamine receptor genes strongly suggest that the common ancestor of Osteichthyes (bony jawed vertebrates) possessed four subtypes in the D1 family and five subtypes in the D2 family. Mammals have secondarily lost almost half of the ancestral dopamine receptor genes, whereas nonmammalian species kept many of them. Although the mammalian situation is an exception among Osteichthyes, the current classification and characterization of dopamine receptors are based on mammalian features, which have led to confusion in the identification of dopamine receptor subtypes in nonmammalian species. Here we begin by reviewing the history of the discovery of dopamine receptors in vertebrates. The recent genome sequencing of coelacanth, gar and elephant shark led to the proposal of a refined scenario of evolution of dopamine receptor genes. We also discuss a current problem of nomenclature of dopamine receptors. Following the official nomenclature of mammalian dopamine receptors from D1 to D5, we propose to name newly identified receptor subtypes from D6 to D9 in order to facilitate the use of an identical name for orthologous genes among different species. To promote a nomenclature change which allows distinguishing the two dopamine receptor families, a nomenclature consortium is needed. This comparative perspective is crucial to correctly interpret data obtained in animal studies on dopamine-related brain disorders, and more fundamentally, to understand the characteristics of dopamine neurotransmission in vertebrates.

scholarly journals The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 139
Author(s):  
Waleed N. Qaddumi ◽  
Pedro A. Jose
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Dopaminergic System ◽  
Receptor Subtypes ◽  
The Many ◽  
Renal Dopamine ◽  
Regulation Of Blood Pressure ◽  
And Oxidative Stress

The kidney is critical in the long-term regulation of blood pressure. Oxidative stress is one of the many factors that is accountable for the development of hypertension. The five dopamine receptor subtypes (D1R–D5R) have important roles in the regulation of blood pressure through several mechanisms, such as inhibition of oxidative stress. Dopamine receptors, including those expressed in the kidney, reduce oxidative stress by inhibiting the expression or action of receptors that increase oxidative stress. In addition, dopamine receptors stimulate the expression or action of receptors that decrease oxidative stress. This article examines the importance and relationship between the renal dopaminergic system and oxidative stress in the regulation of renal sodium handling and blood pressure. It discusses the current information on renal dopamine receptor-mediated antioxidative network, which includes the production of reactive oxygen species and abnormalities of renal dopamine receptors. Recognizing the mechanisms by which renal dopamine receptors regulate oxidative stress and their degree of influence on the pathogenesis of hypertension would further advance the understanding of the pathophysiology of hypertension.

scholarly journals Differential receptor crosstalk in DRD1-DRD2 heterodimer upon phasic and tonic dopamine signals

2021 ◽  
Author(s):  
Hyunbin Kim ◽  
Min-Ho Nam ◽  
Sohyeon Jeong ◽  
Hyowon Lee ◽  
Soo-Jin Oh ◽  
...  
Keyword(s):  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Camp Level ◽  
Receptor Subtypes ◽  
Dopamine Level ◽  
Individual Activity ◽  
Time Activity ◽  
Downstream Signaling ◽  
Receptor Crosstalk

In response to phasic and tonic release, dopamine neurotransmission is regulated by its receptor subtypes, mainly dopamine receptor type 1 and 2 (DRD1 and DRD2). These dopamine receptors are known to form a heterodimer, however the receptor crosstalk between DRD1 and DRD2 was only suspected by measuring their downstream signaling products, due to the lack of methodology for selectively detecting individual activity of different dopamine receptors. Here, we develop red DRD1 sensor (R-DRD1) and green DRD2 sensor (G-DRD2) which can specifically monitor the real-time activity of DRD1 and DRD2, and apply these multicolor sensors to directly measure the receptor crosstalk in the DRD1-DRD2 heterodimer. Surprisingly, we discover that DRD1 activation in the heterodimer is inhibited only at micromolar phasic concentration of dopamine, while DRD2 activation is selectively inhibited at nanomolar tonic dopamine level. Differential receptor crosstalk in the DRD1-DRD2 heterodimer further modulates their downstream cAMP level. These data imply a novel function of the DRD1-DRD2 heterodimer at physiological dopamine levels of phasic and tonic release. Our approach utilizing multicolor receptor sensors will be useful to discover novel function of GPCR heterodimers.

Caffeine mimics dopamine receptor agonists without stimulation of dopamine receptors

1986 ◽  
Vol 25 (6) ◽  
pp. 577-581 ◽  
Author(s):  
H. Watanabe ◽  
H. Uramoto
Keyword(s):  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Dopamine Receptor Agonists ◽  
Receptor Agonists ◽  
Stimulation Of

Pharmacological Characterization of an Adenylyl Cyclase-Coupled 5-HT Receptor in Aplysia: Comparison With Mammalian 5-HT Receptors

2003 ◽  
Vol 89 (3) ◽  
pp. 1440-1455 ◽  
Author(s):  
Jonathan E. Cohen ◽  
Chiadi U. Onyike ◽  
Virginia L. McElroy ◽  
Allison H. Lin ◽  
Thomas W. Abrams
Keyword(s):  
Adenylyl Cyclase ◽  
Rank Order ◽  
Physiological Saline ◽  
Receptor Subtypes ◽  
Pharmacological Profile ◽  
Pharmacological Characterization ◽  
Firing Properties ◽  
Stimulation Of

We attempted to identify compounds that are effective in blocking the serotonin (5-hydroxytryptamine, 5-HT) receptor(s) that activate adenylyl cyclase (AC) in Aplysia CNS. We call this class of receptor 5-HTapAC. Eight of the 14 antagonists tested were effective against 5-HTapAC in CNS membranes with the following rank order of potency: methiothepin > metergoline ∼ fluphenazine > clozapine > cyproheptadine ∼ risperidone ∼ ritanserin > NAN-190. GR-113808, olanzapine, Ro-04-6790, RS-102221, SB-204070, and spiperone were inactive. Methiothepin completely blocked 5-HT stimulation of AC with a K b of 18 nM. Comparison of the pharmacological profile of the 5-HTapAC receptor with those of mammalian 5-HT receptor subtypes suggested it most closely resembles the 5-HT6 receptor. AC stimulation in Aplysia sensory neuron (SN) membranes was also blocked by methiothepin. Methiothepin substantially inhibited two effects of 5-HT on SN firing properties that are mediated by a cAMP-dependent reduction in S-K+ current: spike broadening in tetraethylammonium/nifedipine and increased excitability. Consistent with cyproheptadine blocking 5-HT stimulation of AC, cyproheptadine also blocked the 5-HT-induced increase in SN excitability. Methiothepin was less effective in blocking AC-mediated modulatory effects of 5-HT in electrophysiological experiments on SNs than in blocking AC stimulation in CNS or SN membranes. This reduction in potency appears to be due to effects of the high ionic strength of physiological saline on the binding of this antagonist to the receptor. Methiothepin also antagonized AC-coupled dopamine receptors but not AC-coupled small cardioactive peptide receptors. In conjunction with other pharmacological probes, this antagonist should be useful in analyzing the role of 5-HT in various forms of neuromodulation in Aplysia.

Dopamine Receptors: From Structure to Function

1998 ◽  
Vol 78 (1) ◽  
pp. 189-225 ◽  
Author(s):  
CRISTINA MISSALE ◽  
S. RUSSEL NASH ◽  
SUSAN W. ROBINSON ◽  
MOHAMED JABER ◽  
MARC G. CARON
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adenylyl Cyclase ◽  
Dopamine Receptors ◽  
G Protein ◽  
Receptor Gene ◽  
Hormone Secretion ◽  
Receptor Subtypes ◽  
Genetic Linkage Analysis ◽  
G Protein Coupled

Missale, Cristina, S. Russel Nash, Susan W. Robinson, Mohamed Jaber, and Marc G. Caron. Dopamine Receptors: From Structure to Function. Physiol. Rev. 78: 189–225, 1998. — The diverse physiological actions of dopamine are mediated by at least five distinct G protein-coupled receptor subtypes. Two D1-like receptor subtypes (D1 and D5) couple to the G protein Gs and activate adenylyl cyclase. The other receptor subtypes belong to the D2-like subfamily (D2 , D3 , and D4) and are prototypic of G protein-coupled receptors that inhibit adenylyl cyclase and activate K+ channels. The genes for the D1 and D5 receptors are intronless, but pseudogenes of the D5 exist. The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation. In the central nervous system, dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine secretion. In the periphery, dopamine receptors are present more prominently in kidney, vasculature, and pituitary, where they affect mainly sodium homeostasis, vascular tone, and hormone secretion. Numerous genetic linkage analysis studies have failed so far to reveal unequivocal evidence for the involvement of one of these receptors in the etiology of various central nervous system disorders. However, targeted deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions.

scholarly journals Drugs for psychosis and mood: unique actions at D3, D2, and D1 dopamine receptor subtypes

CNS Spectrums ◽  
2017 ◽  
Vol 22 (5) ◽  
pp. 375-384 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Dopamine Receptor ◽  
D2 Receptors ◽  
Dopamine D2 Receptors ◽  
D1 Receptors ◽  
Receptor Subtypes ◽  
Dopamine Receptor Subtypes ◽  
Dopamine D2 ◽  
D1 Dopamine Receptor ◽  
Serotonin 2A

Drugs for psychosis and mood that bind dopamine D2 receptors can be classified not only by whether they also block serotonin 2A receptors, but by whether they also bind D3 or D1 receptors.

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