Synaptic changes induced by melanocortin signalling

Abstract

The melanocortin system has a well-established role in the regulation of energy homeostasis, but there is growing evidence of its involvement in memory, nociception, mood disorders and addiction. In this Review, we focus on the role of the melanocortin 4 receptor and provide an integrative view of the molecular mechanisms that lead to melanocortin-induced changes in synaptic plasticity within these diverse physiological systems. We also highlight the importance of melanocortin peptides and receptors in chronic pain syndromes, memory impairments, depression and drug abuse, and the possibility of targeting them for therapeutic purposes.

The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances

“…α-MSH was found to potentiate GABA-mediated responses in PVH neurons by acting presynaptically; in addition, the action of α-MSH was blocked by AgRP [40]. The ability to alter synaptic strength may play a role in many functions of melanocortins, including their influence on body weight and reward pathways [41]. However, when stimulated continuously, the MC4R undergoes desensitization and internalization [42] .…”

Evolutionary hierarchy of vertebrate-like heterotrimeric G protein families

“…The signal transduction pathways mediated by G proteincoupled receptors (GPCRs) and their intracellular coupling partner, the heterotrimeric G proteins, are important for several physiological functions including, modulation of synaptic transmission, hormone release, regulation of cell contraction and migration, as well as cell growth and differentiation during development (Cabrera-Vera et al, 2003;Caruso et al, 2014;Civelli et al, 2013;Katritch et al, 2013;Lagerstrom and Schioth, 2008;Malbon, 2005;Melien, 2007;Rosenbaum et al, 2009;Spiegel and Weinstein, 2004;Weinstein et al, 2006;Venkatakrishnan et al, 2013;Wettschureck and Offermanns, 2005). GPCRs contain a seven transmembrane a-helical domain that form a ligand binding pocket and a cytoplasmic domain that interacts with a heterotrimeric G protein complex composed of Ga, Gb, and Gc subunits.…”

Identification of Novel Endogenous Anti(lymph)angiogenic Factors in the Aqueous Humor

“…[16][17][18]22 The a-MSH receptor MSHR1 has been shown to be the only melanocortin receptor expressed on human dermal microvascular endothelial cells. 21,23 Via this receptor, various matrix metalloproteinases (MMPs) are expressed that in turn activate several antiangiogenic factors such as angiostatin, endostatin, or tumstatin. 20 In this work the different in vitro effects of a-MSH were demonstrated.…”