Melanocortin protein receptor

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PT-141, an analog of alpha-MSH exhibits agonist activity at 3 of the 5 known melanocortin receptors]Melanotan II, an analog of alpha-MSH, exhibits agonist activity at 4 of the 5 known melanocortin receptors]
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[b]Subtypes of MCR have been characterized]

* * MC3R, MC4R, and MC5R are known to be expressed in both the central nervous system and in peripheral tissues.

* * MC3R has been found in several nuclei of the hypothalamus, the pancreas, and the gastrointestinal tract;

* * MC4R is found throughout the brain, in the sympathetic nervous system, and in muscle; and

* * MC5R can be found in a broad spectrum of tissues, including the brain and skeletal muscle.

[Semin]

Melanocortins and their receptors and antagonists

Melanocortins are a group of small protein hormones derived by post-translational cleavage of the proopiomelanocortin (POMC) gene product. The known melanocortin hormones include alpha-melanocyte stimulating hormone (MSH), beta-MSH, gamma-MSH and adrenocorticotropic hormone (ACTH). Five melanocortin receptors (MC1R through to MC5R) have been identified and most of these show tissue-specific expression patterns, as well as different binding affinities for each of the melanocortin hormones. The central melanocortin system consists of alpha-MSH, agouti-related protein (AGRP), MC3R and MC4R. AGRP and alpha-MSH are believed to be the natural antagonist and agonist respectively of MC3R and MC4R. This central melanocortin system is thought to play a fundamental role in the control of feeding and body weight. Knock-out mice models and genetic studies have pointed to the importance of the melanocortins in complex human pathways such as pigmentation, lipolysis, food intake, thermogenesis, sexual behaviour, memory and inflammatory response. Recently the melanocortins and their receptors have been the target for drug-based treatment of human physiological processes. MC3R and MC4R are likely targets for controlling body weight; MCIR may be used in the treatment of inflammation and MC2R for the treatment of glucocortical deficiency. A role for MCSR still remains unclear, but the evidence suggests an exocrine gland function.