Involvement of melanocortin receptor accessory proteins (MRAPs) in the function of melanocortin receptors

2013 ◽  
Vol 188 ◽  
pp. 133-136 ◽  
Author(s):  
J.M. Cerdá-Reverter ◽  
M.J. Agulleiro ◽  
R. Cortés ◽  
E. Sánchez ◽  
R. Guillot ◽  
...  
Keyword(s):  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Accessory Proteins

scholarly journals Hypothalamic and Hindbrain Melanocortin Receptors Contribute to the Feeding, Thermogenic, and Cardiovascular Action of Melanocortins

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5351-5361 ◽  
Author(s):  
Karolina P. Skibicka ◽  
Harvey J. Grill
Keyword(s):  
Energy Expenditure ◽  
Nucleus Tractus Solitarius ◽  
Melanocortin Receptor ◽  
Ventrolateral Medulla ◽  
Melanocortin Receptors ◽  
Projection Neurons ◽  
Response Profile ◽  
Feeding Effects ◽  
Retrochiasmatic Area ◽  
Stimulation Of

Abstract Forebrain ventricular delivery of melanocortin receptor (MC3/4R) agonist increases energy expenditure and decreases food intake (FI). Because forebrain ventricular delivery provides ligand to various anatomically distributed MC3/4R-bearing nuclei, it is unclear which of the receptor subpopulations contributes to the feeding suppression and the sympathetic-thermogenic effects observed. The literature indicates that reexpression of MC4R in the paraventricular nucleus (PVH) affects the feeding but not the energetic phenotype of the MC4R knockout, suggesting that divergent MC4R populations mediate energy expenditure (hindbrain) and FI (hypothalamus) effects of stimulation. Not consistent with this view are data indicating that PVH sympathetic projection neurons express MC4Rs and that feeding effects are induced from hindbrain MC4R sites. Therefore, we hypothesize an opposing perspective: that stimulation of anatomically diverse MC3/4R-bearing nuclei triggers energetic as well as feeding effects. To test this hypothesis, ventricle subthreshold doses of MC3/4R agonist (5 and 10 pmol) were applied in separate experiments to six hindbrain and hypothalamic sites; core temperature (Tc), heart rate (HR), spontaneous activity (SPA), and FI were measured in behaving rats. Nucleus tractus solitarius and PVH stimulation increased Tc, HR, and SPA and decreased FI. Rostral ventrolateral medulla, parabrachial nucleus, and retrochiasmatic area stimulation increased Tc, HR, but not SPA, and decreased FI. The response profile differed to some extent for each nucleus tested, suggesting differential output circuitries for the measured parameters. Data are consistent with the view that energetic and feeding responses are not controlled by regionally divergent MC3/4Rs and can be elicited from multiple, anatomically distributed MC3/4R populations.

Activation of central melanocortin-4 receptor suppresses lipopolysaccharide-induced fever in rats

2003 ◽  
Vol 284 (6) ◽  
pp. R1595-R1603 ◽  
Author(s):  
Partha S. Sinha ◽  
Helgi B. Schiöth ◽  
Jeffrey B. Tatro
Keyword(s):  
Systemic Treatment ◽  
Core Body Temperature ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Antipyretic Effect ◽  
Selective Agonist ◽  
Melanocortin 4 Receptor ◽  
Heat Conservation ◽  
Core Body ◽  
Escherichia Coli Lipopolysaccharide

Activation of central melanocortin receptors (MCR) inhibits fever, but the identity of the MCR subtype(s) mediating this antipyretic effect is unknown. To determine whether selective central melanocortin receptor-4 (MC4R) activation produces antipyretic effects, the MC4R selective agonist MRLOB-0001 (CO-His-d-Phe-Arg-Trp-Dab-NH2) was administered intracerebroventricularly to rats treated with Escherichia coli lipopolysaccharide (LPS, 30 μg/kg ip). Treatment with MRLOB-0001 (150 ng icv) did not lower core body temperature (Tc) in afebrile rats but did suppress LPS-induced increases in Tc and associated decreases in tail skin temperature (Tsk), an indicator of vasomotor thermoeffector function. In contrast, systemic treatment with MRLOB-0001 (150 ng iv) did not produce similar antipyretic effects. Coadministration of the selective MC4R antagonist HS014 (1 μg icv) blocked the antipyretic effects of MRLOB-0001. HS014 alone (1 μg icv) had no significant effect on LPS-induced increases in Tc or decreases in Tsk and in afebrile rats had no significant effects on Tc or Tsk. We conclude that pharmacological activation of central MC4R suppresses febrile increases in Tc and that inhibition of heat conservation pathways may contribute to this effect. These findings suggest that the central MC4R may mediate the long-recognized antipyretic effects of centrally administered melanocortins.

scholarly journals The melanocortin receptors and their accessory proteins

2013 ◽  
Vol 4 ◽  
Author(s):  
Shwetha Ramachandrappa ◽  
Rebecca J. Gorrigan ◽  
Adrian J. L. Clark ◽  
Li F. Chan
Keyword(s):  
Melanocortin Receptors ◽  
Accessory Proteins

scholarly journals Melanocortin receptors and their accessory proteins

2011 ◽  
Vol 331 (2) ◽  
pp. 215-221 ◽  
Author(s):  
Sadani N. Cooray ◽  
Adrian J.L. Clark
Keyword(s):  
Melanocortin Receptors ◽  
Accessory Proteins

scholarly journals Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells

2001 ◽  
Vol 5 (1) ◽  
pp. 11-19 ◽  
Author(s):  
KATHLEEN G. MOUNTJOY ◽  
PHILIP L. KONG ◽  
JOHN A. TAYLOR ◽  
DERRIL H. WILLARD ◽  
WILLIAM O. WILKISON
Keyword(s):  
Intracellular Free Calcium ◽  
Melanocortin Receptor ◽  
Hek293 Cells ◽  
Melanocortin Receptors ◽  
Calcium Signal ◽  
Free Calcium ◽  
Agouti Protein ◽  
Transient Rise ◽  
Physiological Relevance ◽  
Free Calcium Concentration

Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either α-melanocyte-stimulating hormone (α-MSH) or desacetyl-α-MSH, mediate increases in intracellular free calcium concentration ([Ca2+]i) with EC50 values between 0.3 and 4.3 nM. The increase in [Ca2+]i is cholera toxin sensitive and pertussis toxin insensitive. The mechanism involves calcium mobilization from intracellular stores without a transient rise in inositol trisphosphate. Mouse agouti protein (55 nM) is a competitive antagonist of α-MSH (6-fold) and desacetyl-α-MSH (8-fold), coupling the mMC1-R to increased [Ca2+]i. Agouti protein (55 nM) significantly increased the EC50 for α-MSH (3-fold), and 550 nM agouti protein significantly increased the EC50 for desacetyl-α-MSH (4-fold), coupling the mMC4-R to a rise in [Ca2+]i. However, agouti protein antagonism of the MC4-R may not be competitive since there was a trend for the maximum response to also increase. There was no significant antagonism of the MC3-R and MC5-R by agouti protein (55 nM). Understanding the physiological relevance of the transduction of a calcium signal by melanocortin peptides may be important for future development of therapeutic targeting of the melanocortin receptors.

scholarly journals MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

2014 ◽  
Vol 52 (3) ◽  
pp. T29-T42 ◽  
Author(s):  
Robert M Dores ◽  
Richard L Londraville ◽  
Jeremy Prokop ◽  
Perry Davis ◽  
Nathan Dewey ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Focal Point ◽  
Cartilaginous Fish ◽  
G Protein Coupled Receptors ◽  
Melanocortin Receptors ◽  
Accessory Proteins ◽  
Melanocortin 1 Receptor ◽  
Ligand Selectivity ◽  
G Protein Coupled ◽  
Receptor Accessory Protein

The melanocortin receptors (MCRs) are a family of G protein-coupled receptors that are activated by melanocortin ligands derived from the proprotein, proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five receptors have become functionally segregated (i.e. melanocortin 1 receptor (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R, energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal–interrenal (HPA–I) axis of teleosts and tetrapods as a result of the exclusive ligand selectivity of MC2R for the ligand ACTH. A second focal point of this review is the roles that the accessory proteins melanocortin 2 receptor accessory protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA–I axis (MC2R) and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of teleosts and tetrapods. In addition, observations are presented on trends in the ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R, MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1–24) when compared with α-MSH. The radiation of the MCRs during the evolution of the gnathostomes provides examples of how the physiology of endocrine and neuronal circuits can be shaped by ligand selectivity, the intersession of reverse agonists (agouti-related peptides (AGRPs)), and interactions with accessory proteins (MRAPs).

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