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Dopamine receptorDopamine 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 primary 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. Additional recommended knowledge
Dopamine receptor subtypes
There are five subtypes of dopamine receptors, D1, D2, D3, D4, and D5. 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. 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 family (excitatory)Activation of 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.
D2-like family (inhibitory)D2-like activation is coupled to the G protein Gαi, which subsequently increases phosphodiesterase activity. Phosphodiesterases break down cAMP, producing an inhibitory effect in neurons.
Role of dopamine receptors in the central nervous systemDopamine receptors control neural signaling that modulates many important behaviors, such as spatial working memory.[4] Non-CNS dopamine receptorsCardio-pulmonary systemIn humans, the pulmonary artery expresses D1, D2, D4, and D5 and receptor subtypes, which may account for vasorelaxive effects of dopamine in the blood.[5] In rats, D1-like receptors are present on the smooth muscle of the blood vessels in most major organs.[6] D4 receptors have been identified in the atria of rat and human hearts.[7] Dopamine increases myocardial contractility and cardiac output, without changing heart rate, by signaling through dopamine receptors.[2] Renal systemDopamine receptors are present along the nephron in the kidney, with proximal tubule epithelial cells showing the highest density.[6] 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.[6] Dopamine signaling affects diuresis and natriuresis.[2] Dopamine receptors in diseaseDysfunction of dopaminergic neurotransmission in the CNS has been implicated in a variety of neuropsychiatric disorders, including Tourette's syndrome,[8] Parkinson's disease,[9] schizophrenia,[8] neuroleptic malignant syndrome[10] Attention-deficit hyperactivity disorder (ADHD),[11] and drug and alcohol dependence.[8][12] Attention-deficit hyperactivity disorderDopamine receptors have been recognized as important components in the etiology of ADHD for many years. Drugs used to treat ADHD, including methylphenidate and amphetamine, have significant effects on dopamine signaling in the brain. Studies of gene association have implicated several genes within dopamine signaling pathways; in particular, the D4.7 variant of D4 has been consistently shown to be more frequent in ADHD patients.[13] ADHD patients with the 4.7 allele also tend to have better cognitive performance and long-term outcomes compared to ADHD patients without the 4.7 allele, suggesting that the allele is associated with a more benign form of ADHD.[13] The D4.7 allele has suppressed gene expression compared to other variants.[14] Recreational drug use and abuseDopamine is the primary neurotransmitter involved in the reward pathways in the brain. Thus, drugs that increase dopamine signaling may produce euphoric effects. Many recreational drugs, such as cocaine and methamphetamine, 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,[15] increased D1[12] and D2[15] receptor signaling mediates the "rewarding" stimulus of drug intake.[15] Reward pathway signaling can affect other regions of the brain as well, inducing long-term changes in regions such as the nucleus accumbens and frontal cortex; these changes can strengthen drug craving and alter cognitive pathways, with drug abuse potentially creating drug addiction and drug dependence. SchizophreniaWhile there is evidence that the dopamine system is involved in schizophrenia, the theory that hyperactive dopaminergic signal transduction induces the disease is controversial. Psychostimulants, such as amphetamine and cocaine, induce dramatic changes in dopamine signaling; large doses and prolonged usage can induce symptoms that resemble schizophrenia. Additionally, many antipsychotic drugs target dopamine receptors, especially D2 receptors. Genetic hypertensionDopamine receptor mutations can cause genetic hypertension in humans.[16] This can occur in animal models and humans with defective dopamine receptor activity, particularly D1.[6] See alsoReferences
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Dopamine_receptor". A list of authors is available in Wikipedia. |
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