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{{BioPsy}}
 
{{BioPsy}}
   
The '''dopamine receptors''' are a class of [[metabotropic receptor|metabotropic]] [[G protein-coupled receptor]]s with the [[neurotransmitter]] [[dopamine]] as their [[endogenous]] [[ligand]].
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[[Image:Dopamine.png|thumb|[[Dopamine]]]]
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'''Dopamine receptors''' are a class of [[metabotropic receptor|metabotropic]] [[G protein-coupled receptor]]s that are prominent in the [[vertebrate]] [[central nervous system]] (CNS). The [[neurotransmitter]] [[dopamine]] is the [[endogenous]] [[ligand]] for dopamine receptors.
   
==Dopamine receptor types==
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Dopamine receptors have key roles in many processes, including the control of motivation, learning, and fine motor movement, as well as modulation of [[neuroendocrine]] signaling. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in [[#Dopamine receptors in disease|several neuropsychiatric disorders]].<ref name="Girault, 2004">{{cite journal |author=Girault J, Greengard P |title=The neurobiology of dopamine signaling |journal=Arch Neurol |volume=61 |issue=5 |pages=641-4 |year=2004 |pmid=15148138}}</ref> Thus, dopamine receptors are common neurologic drug targets; [[antipsychotics]] are often dopamine [[receptor antagonist]]s while [[psychostimulant]]s are typically [[indirect agonist]]s of dopamine receptors.
{| style="border-style: solid; border-width: 1pt; text-align: center; float: right"
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|+align="bottom" style="caption-side: bottom; font-size: small;"|Dopamine receptor agonists (+) and antagonists (-). Specificity is not always perfect. This table is not complete.
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==Dopamine receptor subtypes==
  +
{| style="border-style: solid; border-width: 2pt; text-align: center; float: right"
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|+align="bottom" style="caption-side: bottom; font-size: small;"|Dopamine receptor agonists (+) and antagonists (-). Specificity is not always perfect. This table is not complete.
 
| ||colspan="2" align="center"| D1-like ||style="width:20px"| ||colspan="3" align="center"| D2-like
 
| ||colspan="2" align="center"| D1-like ||style="width:20px"| ||colspan="3" align="center"| D2-like
 
|-
 
|-
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|align=right|[[Raclopride]] || || || ||- ||- ||-
 
|align=right|[[Raclopride]] || || || ||- ||- ||-
 
|-
 
|-
|align=right|[[Clozapine]] ||- ||- || ||- ||- ||'''&mdash;'''
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|align=right|[[Clozapine]] ||- ||- || ||- ||- ||-
 
|-
 
|-
 
|}
 
|}
   
There are five types of dopamine receptor.
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There are five subtypes of dopamine receptors, D1, D2, D3, D4, and D5. D1 and D5 receptors are members of the '''D1-like family''' of dopamine receptors, whereas the D2, D3 and D4 receptors are members of the '''D2-like family'''. There is also some evidence that suggests the existence of possible D6 and D7 dopamine receptors, but such receptors have not been conclusively identified.<ref name="Contreras, 2002">{{cite journal |author=Contreras F, Fouillioux C, Bolívar A, Simonovis N, Hernández-Hernández R, Armas-Hernandez M, Velasco M |title=Dopamine, hypertension and obesity |journal=J Hum Hypertens |volume=16 Suppl 1 |issue= |pages=S13-7 |year=2002 |pmid=11986886}}</ref>
   
The D1 and D5 receptors are members of the D1-like family of dopamine receptors whereas the D2, D3 and D4 receptors are members of the D2-like family.
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===D1-like family===
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Activation of the D1-like family receptors is coupled to the [[G protein]] G<sub>αs</sub>, which subsequently activates [[adenylyl cyclase]], increasing the intracellular concentration of the [[Second messenger system|second messenger]] [[Cyclic adenosine monophosphate]] (cAMP). Increased cAMP in [[neuron]]s is typically excitatory and can induce an [[action potential]] by modulating the activity of [[ion channel]]s.
   
* '''D1-like''': Activation of the D1-like family receptors is coupled to ''increases'' in [[Cyclic adenosine monophosphate|cAMP]] and is typically ''excitatory''.
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====D1====
** D1 ("DRD1", {{OMIM|126449}})
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* D1 ("DRD1", {{OMIM|126449}})
** D5 ("DRD5", {{OMIM|126453}})
 
* '''D2-like''': D2-like activation ''reduces'' cAMP and is typically ''inhibitory''.
 
** D2 ("DRD2", {{OMIM|126450}}). There is a short version of D2 (D2Sh) and a long version of D2 (D2Lh). The D2Sh are pre-synaptic situated, having modulatory functions (called [[autoreceptor]], they regulates the neurotransmission by feed-back mechanisms, i.e., synthesis, storage and release of [[dopamine]] into the [[synaptic cleft]]) and the D2Lh, which may have the classic function of a post-synaptic receptor, i.e., keep going on the neurotransmission (excitatory or inhibitory) once blocked by a [[receptor antagonist]] or stimulated by the endogenous [[neurotransmitter]] itself or a synthetic full or partial [[agonist]].
 
** D3 ("DRD3", {{OMIM|126451}})
 
** D4 ("DRD4", {{OMIM|126452}}). D4 has the following variants D4.2, D4.3a, D4.3b, D4.4a, D4.4b, D4.4c, D4.4d, D4.4e, D4.5a, D4.5b, D4.6a, D4.6b, D4.7a, D4.7b, D4.7c, D4.7d, D4.8, D4.10.
 
   
All are G protein coupled metabotropic receptors, and can be excitatory or inhibitory to the post-synaptic neuron.
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====D5====
  +
* D5 ("DRD5", {{OMIM|126453}})
   
In [[schizophrenia|schizophrenics]] and patients with [[Tardive dysphrenia]], D2 receptors are supposed to exist in higher than normal levels on the dopaminergic [[mesolimbic pathway]], and [[antipsychotic drugs]] which aim to block these may cause its [[upregulation]].
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===D2-like family===
  +
D2-like activation is coupled to the [[G protein]] G<sub>αi</sub>, which subsequently increased [[phosphodiesterase]] activity. Phosphodiesterases break down cAMP, producing an inhibitory effect in neurons.
   
In patients with Tourettes Syndrome, studies show that the severity of the patient's tics may be directly correlated with the amount of binding of D2 Dopamine receptors in the Caudate nucleus.
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====D2====
  +
*D2 ("DRD2", {{OMIM|126450}}). There is a short version of D2 (D2Sh) and a long version of D2 (D2Lh):
  +
** The ''D2Sh'' are pre-synaptic situated, having modulatory functions (called [[autoreceptor]], they regulate the neurotransmission by feed-back mechanisms, i.e., synthesis, storage and release of [[dopamine]] into the [[synaptic cleft]]) .
  +
** The ''D2Lh'' may have the classic function of a post-synaptic receptor, i.e., keep going on the neurotransmission (excitatory or inhibitory) once blocked by a [[receptor antagonist]] or stimulated by the endogenous [[neurotransmitter]] itself or a synthetic full or partial [[agonist]].
   
== References ==
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====D3====
* Zimmerberg, B., [http://www.williams.edu/imput/IIIB1.html "Dopamine receptors: A representative family of metabotropic receptors], Multimedia Neuroscience Education Project (2002)
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* D3 ("DRD3", {{OMIM|126451}})
   
* FROTA LH. [http://www.medicina.ufrj.br/cursos/JBP%202%20COLUNAS%20-%20com%20referencia%20completa%20&%20foto%20-%20AGONISTAS%20PARCIAIS%20NO%20ARMAMENTARIUM.pdf "Partial Agonists in the Schizophrenia Armamentarium. Tardive Dysphrenia: The newest challenge to the last generation atypical antipsychotics drugs?"] J Bras Psiquiatr 2003; Vol 52 Supl 1;14-24.
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====D4====
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* D4 ("DRD4", {{OMIM|126452}}). D4 has the following variants D4.2, D4.3a, D4.3b, D4.4a, D4.4b, D4.4c, D4.4d, D4.4e, D4.5a, D4.5b, D4.6a, D4.6b, D4.7a, D4.7b, D4.7c, D4.7d, D4.8, D4.10.
  +
  +
==Role of dopamine receptors in the central nervous system==
  +
Dopamine receptors control neural signaling that modulates many important behaviors, such as [[Spatial memory|spatial]] [[working memory]].<ref name="Williams, 2006">{{cite journal |author=Williams G, Castner S |title=Under the curve: critical issues for elucidating D1 receptor function in working memory |journal=Neuroscience |volume=139 |issue=1 |pages=263-76 |year=2006 |pmid=16310964}}</ref>
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  +
==Non-CNS dopamine receptors==
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===Cardio-pulmonary system===
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In humans, the [[pulmonary artery]] expresses D1, D2, D4, and D5 and receptor subtypes, which may account for [[Vasodialation|vasorelaxive]] effects of dopamine in the blood.<ref name="Ricci, 2006">{{cite journal |author=Ricci A, Mignini F, Tomassoni D, Amenta F |title=Dopamine receptor subtypes in the human pulmonary arterial tree |journal=Auton Autacoid Pharmacol |volume=26 |issue=4 |pages=361-9 |year=2006 |pmid=16968475}}</ref> In [[rat]]s, D1-like receptors are present on the [[smooth muscle]] of the [[blood vessel]]s in most major organs.<ref name="Hussain, 2003">{{cite journal |author=Hussain T, Lokhandwala M |title=Renal dopamine receptors and hypertension |journal=Exp Biol Med (Maywood) |volume=228 |issue=2 |pages=134-42 |year=2003 |pmid=12563019}}</ref>
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  +
D4 receptors have been identified in the [[Atrium (heart)|atria]] of rat and human [[heart]]s.<ref name="Ricci, 1998">{{cite journal |author=Ricci A, Bronzetti E, Fedele F, Ferrante F, Zaccheo D, Amenta F |title=Pharmacological characterization and autoradiographic localization of a putative dopamine D4 receptor in the heart |journal=J Auton Pharmacol |volume=18 |issue=2 |pages=115-21 |year=1998 |pmid=9730266}}</ref> Dopamine increases [[myocardial]] contractility and [[cardiac output]], without changing [[heart rate]], by signaling through dopamine receptors.<ref name="Contreras, 2002"/>
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===Renal system===
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Dopamine receptors are present along the [[nephron]] in the [[kidney]], with [[proximal tubule]] [[epithelial cell]]s showing the highest density.<ref name="Hussain, 2003"/> In [[rat]]s, D1-like receptors are present on the [[juxtaglomerular apparatus]] and on [[renal tubules]], while D2-like receptors are present on the renal tubules, [[glomeruli]], postganglionic [[sympathetic nerve]] terminals, and [[zona glomerulosa]] cells of the renal cortex.<ref name="Hussain, 2003"/> Dopamine signaling affects [[diuresis]] and [[natriuresis]].<ref name="Contreras, 2002"/>
  +
  +
==Dopamine receptors in disease==
  +
Dysfunction of dopaminergic neurotransmission in the CNS has been implicated in a variety of neuropsychiatric disorders, including [[Tourette's syndrome]],<ref name="Kienast, 2006">{{cite journal |author=Kienast T, Heinz A |title=Dopamine and the diseased brain |journal=CNS Neurol Disord Drug Targets |volume=5 |issue=1 |pages=109-31 |year=2006 |pmid=16613557}}</ref> [[Parkinson's disease]],<ref name="Fuxe, 2006">{{cite journal |author=Fuxe K, Manger P, Genedani S, Agnati L |title=The nigrostriatal DA pathway and Parkinson's disease |journal=J Neural Transm Suppl |volume=70 |issue= |pages=71-83 |year=2006 |pmid=17017512}}</ref> [[schizophrenia]],<ref name="Kienast, 2006"/> [[Attention-deficit hyperactivity disorder]],<ref name="Faraone, 2006">{{cite journal |author=Faraone S, Khan S |title=Candidate gene studies of attention-deficit/hyperactivity disorder |journal=J Clin Psychiatry |volume=67 Suppl 8 |issue= |pages=13-20 |year=2006 |pmid=16961425}}</ref> and [[drug]] and [[alcohol]] [[Physical dependence|dependence]].<ref name="Kienast, 2006"/><ref name="Hummel, 2002"/>
  +
  +
===Drug abuse===
  +
Dopamine is the primary neurotransmitter involved in the reward pathways in the brain. Thus, drugs that increase dopmamine signaling may produce euphoric effects. [[Cocaine]] and [[methamphetamine]]&mdash;two examples of such drugs&mdash;alter the functionality of the [[dopamine transporter]] (DAT), the protein responsible for removing dopamine from the neural [[synapse]]. When DAT activity is blocked, the synapse floods with dopamine and increases dopaminergic signaling. When this occurs, particularly in the [[nucleus accumbens]],<ref name="Di Chiara, 2004">{{cite journal |author=Di Chiara G, Bassareo V, Fenu S, De Luca M, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D |title=Dopamine and drug addiction: the nucleus accumbens shell connection |journal=Neuropharmacology |volume=47 Suppl 1 |issue= |pages=227-41 |year=2004 |pmid=15464140}}</ref> increased D1<ref name="Hummel, 2002">{{cite journal |author=Hummel M, Unterwald E |title=D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action |journal=J Cell Physiol |volume=191 |issue=1 |pages=17-27 |year=2002 |pmid=11920678}}</ref> and D2<ref name="Di Chiara, 2004"/> receptor signaling mediates the "rewarding" stimulus of drug intake.<ref name="Di Chiara, 2004"/>
  +
  +
===Genetic hypertension===
  +
Dopamine receptor [[mutation]]s can cause genetic [[hypertension]] in humans.<ref name="Jose, 2003">{{cite journal |author=Jose P, Eisner G, Felder R |title=Regulation of blood pressure by dopamine receptors |journal=Nephron Physiol |volume=95 |issue=2 |pages=p19-27 |year=2003 |pmid=14610323}}</ref> This can occur in [[animal model]]s and humans with defective dopamine receptor activity, particularly D1.<ref name="Hussain, 2003"/>
   
 
== External links ==
 
== External links ==
 
*[http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1282 IUPHAR GPCR Database - Dopamine Receptors]
 
*[http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1282 IUPHAR GPCR Database - Dopamine Receptors]
  +
*Zimmerberg, B., [http://www.williams.edu/imput/IIIB1.html "Dopamine receptors: A representative family of metabotropic receptors], Multimedia Neuroscience Education Project (2002)
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== References ==
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<!--See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for an explanation of how to generate footnotes using the <ref> and </ref> tags and the tag below -->
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{{Reflist|2}}
   
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{{G protein-coupled receptors}}
 
[[Category:G protein coupled receptors]]
 
[[Category:G protein coupled receptors]]
   
[[de: Dopamin-Rezeptor]]
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:de:Dopamin-Rezeptor
[[ja:ドパミン受容体]]
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:ja:ドパミン受容体
 
{{enWP|Dopamine receptors}}
 
{{enWP|Dopamine receptors}}

Latest revision as of 14:10, March 28, 2007

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Dopamine

Dopamine

Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). The neurotransmitter dopamine is the endogenous ligand for dopamine receptors.

Dopamine receptors have key roles in many processes, including the control of motivation, learning, and fine motor movement, as well as modulation of neuroendocrine signaling. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders.[1] Thus, dopamine receptors are common neurologic drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors.

Dopamine receptor subtypesEdit

Dopamine receptor agonists (+) and antagonists (-). Specificity is not always perfect. This table is not complete.
D1-like D2-like
D1 D5 D2 D3 D4
Apomorphine + + + + +
Fenoldopam + + + ? +
SKF 38393 + + +
SKF 82958 + +
Dihydrexidine + +
Quinpirole + +
Haloperidol - ? - - ?
Flupentixol - ? - ? ?
Fluphenazine - ? ? ? ?
SCH 23390 - -
Spiperone ? - ? ?
Raclopride - - -
Clozapine - - - - -

There are five subtypes of dopamine receptors, D1, D2, D3, D4, and D5. D1 and D5 receptors are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 receptors are members of the D2-like family. There is also some evidence that suggests the existence of possible D6 and D7 dopamine receptors, but such receptors have not been conclusively identified.[2]

D1-like familyEdit

Activation of the D1-like family receptors is coupled to the G protein Gαs, which subsequently activates adenylyl cyclase, increasing the intracellular concentration of the second messenger Cyclic adenosine monophosphate (cAMP). Increased cAMP in neurons is typically excitatory and can induce an action potential by modulating the activity of ion channels.

D1Edit

D5Edit

D2-like familyEdit

D2-like activation is coupled to the G protein Gαi, which subsequently increased phosphodiesterase activity. Phosphodiesterases break down cAMP, producing an inhibitory effect in neurons.

D2Edit

  • D2 ("DRD2", OMIM 126450). There is a short version of D2 (D2Sh) and a long version of D2 (D2Lh):
    • The D2Sh are pre-synaptic situated, having modulatory functions (called autoreceptor, they regulate the neurotransmission by feed-back mechanisms, i.e., synthesis, storage and release of dopamine into the synaptic cleft) .
    • The D2Lh may have the classic function of a post-synaptic receptor, i.e., keep going on the neurotransmission (excitatory or inhibitory) once blocked by a receptor antagonist or stimulated by the endogenous neurotransmitter itself or a synthetic full or partial agonist.

D3Edit

D4Edit

  • D4 ("DRD4", OMIM 126452). D4 has the following variants D4.2, D4.3a, D4.3b, D4.4a, D4.4b, D4.4c, D4.4d, D4.4e, D4.5a, D4.5b, D4.6a, D4.6b, D4.7a, D4.7b, D4.7c, D4.7d, D4.8, D4.10.

Role of dopamine receptors in the central nervous systemEdit

Dopamine receptors control neural signaling that modulates many important behaviors, such as spatial working memory.[3]

Non-CNS dopamine receptorsEdit

Cardio-pulmonary systemEdit

In humans, the pulmonary artery expresses D1, D2, D4, and D5 and receptor subtypes, which may account for vasorelaxive effects of dopamine in the blood.[4] In rats, D1-like receptors are present on the smooth muscle of the blood vessels in most major organs.[5]

D4 receptors have been identified in the atria of rat and human hearts.[6] Dopamine increases myocardial contractility and cardiac output, without changing heart rate, by signaling through dopamine receptors.[2]

Renal systemEdit

Dopamine receptors are present along the nephron in the kidney, with proximal tubule epithelial cells showing the highest density.[5] In rats, D1-like receptors are present on the juxtaglomerular apparatus and on renal tubules, while D2-like receptors are present on the renal tubules, glomeruli, postganglionic sympathetic nerve terminals, and zona glomerulosa cells of the renal cortex.[5] Dopamine signaling affects diuresis and natriuresis.[2]

Dopamine receptors in diseaseEdit

Dysfunction of dopaminergic neurotransmission in the CNS has been implicated in a variety of neuropsychiatric disorders, including Tourette's syndrome,[7] Parkinson's disease,[8] schizophrenia,[7] Attention-deficit hyperactivity disorder,[9] and drug and alcohol dependence.[7][10]

Drug abuseEdit

Dopamine is the primary neurotransmitter involved in the reward pathways in the brain. Thus, drugs that increase dopmamine signaling may produce euphoric effects. Cocaine and methamphetamine—two examples of such drugs—alter the functionality of the dopamine transporter (DAT), the protein responsible for removing dopamine from the neural synapse. When DAT activity is blocked, the synapse floods with dopamine and increases dopaminergic signaling. When this occurs, particularly in the nucleus accumbens,[11] increased D1[10] and D2[11] receptor signaling mediates the "rewarding" stimulus of drug intake.[11]

Genetic hypertensionEdit

Dopamine receptor mutations can cause genetic hypertension in humans.[12] This can occur in animal models and humans with defective dopamine receptor activity, particularly D1.[5]

External links Edit

References Edit

  1. Girault J, Greengard P (2004). The neurobiology of dopamine signaling. Arch Neurol 61 (5): 641-4.
  2. 2.0 2.1 2.2 Contreras F, Fouillioux C, Bolívar A, Simonovis N, Hernández-Hernández R, Armas-Hernandez M, Velasco M (2002). Dopamine, hypertension and obesity. J Hum Hypertens 16 Suppl 1: S13-7.
  3. Williams G, Castner S (2006). Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience 139 (1): 263-76.
  4. Ricci A, Mignini F, Tomassoni D, Amenta F (2006). Dopamine receptor subtypes in the human pulmonary arterial tree. Auton Autacoid Pharmacol 26 (4): 361-9.
  5. 5.0 5.1 5.2 5.3 Hussain T, Lokhandwala M (2003). Renal dopamine receptors and hypertension. Exp Biol Med (Maywood) 228 (2): 134-42.
  6. Ricci A, Bronzetti E, Fedele F, Ferrante F, Zaccheo D, Amenta F (1998). Pharmacological characterization and autoradiographic localization of a putative dopamine D4 receptor in the heart. J Auton Pharmacol 18 (2): 115-21.
  7. 7.0 7.1 7.2 Kienast T, Heinz A (2006). Dopamine and the diseased brain. CNS Neurol Disord Drug Targets 5 (1): 109-31.
  8. Fuxe K, Manger P, Genedani S, Agnati L (2006). The nigrostriatal DA pathway and Parkinson's disease. J Neural Transm Suppl 70: 71-83.
  9. Faraone S, Khan S (2006). Candidate gene studies of attention-deficit/hyperactivity disorder. J Clin Psychiatry 67 Suppl 8: 13-20.
  10. 10.0 10.1 Hummel M, Unterwald E (2002). D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action. J Cell Physiol 191 (1): 17-27.
  11. 11.0 11.1 11.2 Di Chiara G, Bassareo V, Fenu S, De Luca M, Spina L, Cadoni C, Acquas E, Carboni E, Valentini V, Lecca D (2004). Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 47 Suppl 1: 227-41.
  12. Jose P, Eisner G, Felder R (2003). Regulation of blood pressure by dopamine receptors. Nephron Physiol 95 (2): p19-27.
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