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Cocaine and amphetamine regulated transcript

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Cocaine and amphetamine regulated transcript also known as CART is a protein which in humans is encoded by the CARTPT gene.[1][2] CART appears to have roles in reward, feeding, and stress, and it has the functional properties of an endogenous psychostimulant.[3]

Function Edit

CART is a neuropeptide which also serves as a neurotransmitter. It elicits similar behaviour as cocaine and amphetamine. The peptide is found in several areas, among them ventral tegmental area (VTA). (VTA) has been connected to "feelings of euphoria". When injected into rat-(VTA), increased locomotor activity is seen. Increased locomotor activity is one of the signs of "central stimulation" caused by substances such as cocaine and amphetamine. The rats tended to return to the place where they had been injected. This is called conditioned place preference and is seen after injection of cocaine. This has led to speculation that CART could be an "endogenous cocaine". CART also is found at the same locations where cocaine and methamphetamine tend to act.[4]

CART peptides, particularly CART (55–102), seems to have an important function in the regulation of energy homeostasis and interacts with several central appetite circuits. CART expression is regulated by many peripheral factors, one of them leptin.[5]

Tissue distribution Edit

CART is an anorexigenic peptide and is widely expressed in both the central and peripheral nervous systems, particularly concentrated in the hypothalamus. CART is outside of the nervous system also expressed in pituitary endocrine cells, adrenomedullary cells, islet somatostatin cells, and in rat antral gastrin cells.[6]

Clinical significance Edit

Based on studies of CART (54–102) action in rat lateral ventricle and amygdala suggest that CART play a role in anxiety-like behavior, induced by ethanol withdrawal in rats.[7] Studies on CART knock-out mice indicates that CART modulates the locomotor, conditioned place preference and cocaine self-administration effect of psychostimulants. This suggests a positive neuromodulatory action of CART on psychostimulants effect on rat.[8] CART is altered in the ventral tegmental area of cocaine overdose victims, and a mutation in the CART gene associates with alcoholism.[9] CART peptides are inhibitors of food intake (anorexigenic) and closely associated with leptin and neuropeptide Y, two important food intake regulators. CART peptides are also involved in fear and startle behavior.[10]

History Edit

CART was found by examining changes in the brain following cocaine or amphetamine administration. CART mRNA increased with cocaine administration. One of the goals was to find an endogenous anorexigenic substance. CART inhibited rat food intake by as much as 30 percent. When naturally-occurring CART peptides were blocked by means of injecting antibodies to CART, feeding increased. This led to suggestions CART may play a role - though not being the only peptide - in satiety. In the end of 1980th's, researchers started to synthesize cocaine- and CART-like-acting substances in order to find medications that could affect eating disorders as well as cocaine abuse. These cocaine-like substances are called phenyltropanes.[11]

ReferencesEdit

  1. Douglass J, Daoud S (March 1996). Characterization of the human cDNA and genomic DNA encoding CART: a cocaine- and amphetamine-regulated transcript. Gene 169 (2): 241–5.
  2. Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S (May 1998). Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393 (6680): 72–6.
  3. Kuhar MJ, Adams S, Dominguez G, Jaworski J, Balkan B (February 2002). CART peptides. Neuropeptides 36 (1): 1–8.
  4. Brain Contains Cocaine-Like Chemical. ScienceDaily LLC. URL accessed on 2009-02-10.
  5. Murphy KG (July 2005). Dissecting the role of cocaine- and amphetamine-regulated transcript (CART) in the control of appetite. Brief Funct Genomic Proteomic 4 (2): 95–111.
  6. Wierup N, Kuhar M, Nilsson BO, Mulder H, Ekblad E, Sundler F (February 2004). Cocaine- and amphetamine-regulated transcript (CART) is expressed in several islet cell types during rat development. J. Histochem. Cytochem. 52 (2): 169–77.
  7. Dandekar MP, Singru PS, Kokare DM, Lechan RM, Thim L, Clausen JT, Subhedar NK (April 2008). Importance of cocaine- and amphetamine-regulated transcript peptide in the central nucleus of amygdala in anxiogenic responses induced by ethanol withdrawal. Neuropsychopharmacology 33 (5): 1127–36.
  8. Couceyro PR, Evans C, McKinzie A, Mitchell D, Dube M, Hagshenas L, White FJ, Douglass J, Richards WG, Bannon AW (December 2005). Cocaine- and amphetamine-regulated transcript (CART) peptides modulate the locomotor and motivational properties of psychostimulants. J. Pharmacol. Exp. Ther. 315 (3): 1091–100.
  9. Kuhar MJ, Jaworski JN, Hubert GW, Philpot KB, Dominguez G (2005). Cocaine- and amphetamine-regulated transcript peptides play a role in drug abuse and are potential therapeutic targets. AAPS J 7 (1): E259–65.
  10. CART (Cocaine- and Amphetamine-Regulated Transcript) Peptides. anaspec.com. URL accessed on 2009-02-10.
  11. Cocaine Studies Reveal New Medications For Addiction; How Brain Regulates Hunger. ScienceDaily LLC. URL accessed on 2009-02-11.

See alsoEdit

External linksEdit


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