Investigation of the melanocyte stimulating hormones on food intake: Lack of evidence to support a role for the melanocortin-3-receptor

• Published in: Brain research 2000-06, Vol.869 (1), p.203-210
• Main Authors: Abbott, Caroline R, Rossi, Michela, Kim, Min-Seon, AlAhmed, Samaher H, Taylor, Gillian M, Ghatei, Mohammad A, Smith, David M, Bloom, Stephen R
• Format: Article
• Language: English
• Subjects: alpha-MSH - metabolism; alpha-MSH - pharmacology; Animals; Appetite; beta-MSH - metabolism; beta-MSH - pharmacology; Biological and medical sciences; Brain - cytology; Brain - drug effects; Brain - metabolism; Cell Line; Cyclic AMP - metabolism; Eating - drug effects; Eating - physiology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; gamma-MSH - metabolism; gamma-MSH - pharmacology; Hypothalamus; Intracerebroventricular; Male; Melanocortin receptors; Melanocyte stimulating hormone; Melanocyte-Stimulating Hormones - metabolism; Melanocyte-Stimulating Hormones - pharmacology; Radioligand Assay; Rats; Rats, Wistar; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Receptors, Corticotropin - drug effects; Receptors, Corticotropin - metabolism; Receptors, Peptide - drug effects; Receptors, Peptide - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02386-6

The melanocortin receptors, melanocortin-3-receptor (MC3-R) and melanocortin-4-receptor (MC4-R), are expressed in many discrete medial hypothalamic nuclei implicated in feeding regulation. The pro-opiomelanocortin product α-melanocyte stimulating hormone (α-MSH), an MC3/4-R agonist, decreases food intake following intracerebroventricular (ICV) injection in rats. MC4-R’s involvement in feeding has been established although a function for the MC3-R is unclear. We investigated endogenous melanocortin ligand binding and activation at the MC3-R and MC4-R and their effects on feeding. We have shown that α-MSH, desacetyl-α-MSH and β-MSH bound to the MC3-R and MC4-R with similar affinity and stimulated cAMP with similar potency in HEK 293 cells transfected with MC3-R and MC4-R. In contrast γ 2-MSH showed selectivity for the MC3-R over the MC4-R both in binding affinity and cAMP stimulation. α-MSH and β-MSH injected ICV into fasted rats at doses of 1, 3 and 6 nmol resulted in a decrease in food intake, (2 h food intake: α-MSH 6 nmol, 1.7±0.3 g; β-MSH 6 nmol, 1.5±0.3 g vs. saline 6.0±0.5 g, P