Abstract
Increasing evidence indicates that the melanocortin system is not only a central player in energy homeostasis, food intake and glucose level regulation, but also in the modulation of cardiovascular functions, such as blood pressure and heart rate. The melanocortins, and in particular α- and γ-MSH, have been shown to exert their cardiovascular activity both at the central nervous system level and in the periphery (e.g., in the adrenal gland), binding their receptors MC3R and MC4R and influencing the activity of the sympathetic nervous system. In addition, some studies have shown that the activation of MC3R and MC4R by their endogenous ligands is able to improve the outcome of cardiovascular diseases, such as myocardial and cerebral ischemia. In this brief review, we will discuss the current knowledge of how the melanocortin system influences essential cardiovascular functions, such as blood pressure and heart rate, and its protective role in ischemic events, with a particular focus on the central regulation of such mechanisms.
Highlights
THE MELANOCORTIN SYSTEM AND CARDIOVASCULAR FUNCTIONSThe melanocortin system consists of several melanocortin peptides and their receptors expressed in the brain, as well as in the periphery
Specialty section: This article was submitted to Integrative Physiology, a section of the journal Frontiers in Physiology
POMC expressing neurons are predominantly located in the arcuate nucleus (ARC) of the hypothalamus and the nucleus tractus solitarius (NTS) of the brainstem (Young et al, 1998)
Summary
The melanocortin system consists of several melanocortin peptides and their receptors expressed in the brain, as well as in the periphery. In the central nervous system (CNS), the proopiomelanocortin (POMC) neurons produce several peptides by post-translational modification, such as adrenocorticotrophin (ACTH), α-,β-, and γ-melanocyte stimulating hormone (α-MSH, β-MSH, and γ-MSH), and β-endorphin (Smith and Funder, 1988). These melanocortin peptides bind to five melanocortin receptor subtypes (MC1R-MC5R) with differential binding affinity (Kim et al, 2002). Α-MSH is the most well-known anorexigenic peptide, able to inhibit food intake and increase energy expenditure mainly through central MC4R activation (Ollmann et al, 1997). The activity of POMC neurons is opposed by Neuropeptide Y/Agouti-related peptide (NPY/AgRP) expressing neurons, which produce the MC3R and MC4R inverse agonist AgRP (Ollmann et al, 1997)
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