CART (Cocaine- and Amphetamine-Regulated Transcript) Peptides

Definition

Cocaine- and amphetamine- regulated transcript (CART) peptides, derived from proCART polypeptide in humans are neuropeptides expressed in the brain1. They mainly serve as inhibitors of food intake1.

Discovery

CART was first purified by gel filtration and sequenced in 1980 from rat hypothalamus2.

Classification

CART is a neuropeptide family member2.

Structural Characteristics

CART gene encodes a peptide of either 129 or 116 amino acid residues in rat whereas only the short form exists in humans. The predicted signal sequence is 27 amino acid residues resulting in a precursor of 102 or 89 residues3. The C-terminal end of CART, consisting of 48 amino acid residues and 3 disulphide bonds, is thought to constitute a biologically active part of the molecule. Various CART peptides can be generated from the precursor: CARTs (55-102), (85-102), (55-76) and (62-76)3. CART (55-102) contains three disulphide bridges that are required for its function4.



Mode of action

The mode of action of CART peptides has not been fully established. Several studies have observed that they may function through CART receptors in turn activating down stream signaling pathways5.



Functions

CART is distributed in the central nervous system and periphery and has many physiological roles. It elicits similar behavior as cocaine. CART has been shown to have variety of effects on dopamine6. It increases blood pressure, has variety of behavioral effects and influences nociception6. In the hypothalamus CART mainly regulates energy homeostasis6. CART is also an endogenous inhibitor of food intake6. CART peptides are also important in anxiety, pain, arousal, startle response, regulation of calcium channels, and neuroendocrine hormone secretion5.





References



1. Thim L, Kristensen P, Larsen PJ, Wulff BS (1998). CART, a new anorectic peptide. Int J Biochem Cell Biol, 30(12), 1281-4.

2. Spiess J and Vale W (1980). Multiple forms of somatostatin-like activity in rat hypothalamus. Biochemistry 19, 2861–66.

3. Dylag T, Kotlinska J, Rafalski P, Pachuta A, Silberring J (2006). The activity of CART peptide fragments. Peptides, 27(8), 1926-33.

4. Murphy KG (2005). Dissecting the role of cocaine and amphetamine-regulated transcript (CART) in the control of appetite. Briefing in Functional Genomics and proteomic, 4 (2), 95–111.

5. Rogge G, Jones D, Hubert GW, Lin Y & Kuhar MJ (2008). CART peptides: regulators of body weight, reward and other functions. Nature Reviews Neuroscience, 9, 747-758.

6. Vicentic A, Jones DC (2007). The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction. J Pharmacol Exp Ther., 320(2), 499-506.