Dopamine receptor

Dopamine receptors are implicated in many neurological processes, including motivational and incentive salience, cognition, memory, learning, and fine motor control, as well as modulation of neuroendocrine signaling.

Gsα subsequently activates adenylyl cyclase, increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP).

Dopamine receptors may also regulate ion channels and BDNF independent of cAMP, possibly through direct interactions.

There is evidence that D1 receptor agonism regulates phospholipase C independent of cAMP, however implications and mechanisms remain poorly understood.

[19] Beta Arrestin recruitment is mediated by G-protein kinases that phosphorylate and inactivate dopamine receptors after stimulation.

Dopamine receptor D2 stimulation results in the formation of an Akt/Beta-arrestin/PP2A protein complex that inhibits Akt through PP2A phosphorylation, therefore disinhibiting GSK-3.

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

[21] Dopamine also plays an important role in the reward system, incentive salience, cognition, prolactin release, emesis and motor function.

[22] In humans, the pulmonary artery expresses D1, D2, D4, and D5 and receptor subtypes, which may account for vasodilatory effects of dopamine in the blood.

[5] Dopamine receptors are present along the nephron in the kidney, with proximal tubule epithelial cells showing the highest density.

Pancreatic endocrine glands, composed of dense clusters of cells called the Islets of Langerhans, secrete insulin, glucagon, and other hormones essential for metabolism and glycemic control.

[37] Dopamine receptors D1, D2, D4, and D5 are present in human subcutaneous, visceral, and brown adipose tissue, and have been implicated in lipid and glucose metabolism, and thermogenesis[38][39].

Dopamine that reaches dopamine receptors in adipose tissue can originate from multiple sources: from the circulation, sympathetic nerves innervating adipose tissue that release dopamine from nerve terminals, local synthesis, or immune cells[40][41] Dysfunction of dopaminergic neurotransmission in the CNS has been implicated in a variety of neuropsychiatric disorders, including social phobia,[42] Tourette's syndrome,[43] Parkinson's disease,[44] schizophrenia,[43] neuroleptic malignant syndrome,[45] attention-deficit hyperactivity disorder (ADHD),[46] and drug and alcohol dependence.

[55] While 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, indirectly increase dopamine signaling; large doses and prolonged use can induce symptoms that resemble schizophrenia.

[55] Parkinson's disease patients are treated with medications which help to replenish dopamine availability, allowing relatively normal brain function and neurotransmission.

[61] Haloperidol increased the number of binding sites by 98% above baseline in the worst cases, and yielded significant dyskinesia side effects.

[64][65] A recent news article[66] summarized a U.S. DOE Brookhaven National Laboratory study showing that increasing dopamine receptors with genetic therapy temporarily decreased cocaine consumption by up to 75%.

[69] Certain stimulants will enhance cognition in the general population (e.g., direct or indirect mesocortical DRD1 agonists as a class), but only when used at low (therapeutic) concentrations.