Agonists and antagonists to the melanocortin receptors MC4R and MC3R
are among the most powerful drugs for changing body weight in rodents, but application to humans has not been successful because of strong undesirable side effects.
In the brain, the most abundant MCR subtypes are MC3R
and MC4R [35,36].
Taheri, "Association of CTSZ rs34069356 and MC3R
rs6127698 gene polymorphisms with pulmonary tuberculosis," The International Journal of Tuberculosis and Lung Disease, vol.
[alpha]-MSH regulates food intake and energy homeostasis by acting on melanocortin-3 receptors (MC3R
) and melanocortin-4 receptors (MC4R).
These effects are caused by a-MSH interacting with its specific membrane receptors: MC1R, MC2R, MC3R
, MC4R, and MC5R.
These peptides act on the melanocortin receptors (MCR), chiefly MC4R and MC3R
, distributed throughout the central nervous system.
Alpha-melanocyte-stimulating hormone ([alpha]-MSH) is a potent anorexigenic neuropeptide (5); leptin stimulates the production of [alpha]-MSH, which is an agonist for melanocortin-4 receptors (MC4R) and melanocortin-3 receptors (MC3R
), and inhibits the production of AgRP (an antagonist for these receptors) in a coordinated manner to regulate the energy balance by inhibiting food intake and stimulating energy expenditure (6).
aMSH modulates its downstream homeostatic signalling via their action at melanocortin receptors MC3R
and MC4R, which are antagonized by AgRP .
The study focused on the melanocortin-3 receptor (MC3R
), which normally responds to signals of nutrient intake.
(4) Recently, obesity-related mutations (A293T, I335S, X361S, I183, A70T and M134I) have been identified in the melanocortin-3 receptor gene (MC3R
) - another energy-regulating melanocortin receptor.
Functional study showed that AgRp and Mc3r
were significantly upregulated in the neuron specific Lpl knock-out mice .