The agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic (appetite-stimulating) activity. The cysteine-rich C-terminal domain of this protein, corresponding to AGRP(87-132), contains five disulfide bonds and exhibits receptor binding affinity and antagonism equivalent to that of the full-le...

Macrophages have crucial functions in initiating the inflammatory reaction in a strict temporal and spatial manner to provide a "clear-up" response required for resolution. Hormonal peptides such as melanocortins modulate macrophage reactivity and attenuate inflammation ranging from skin inflammation to joint disease and reperfusion injury. The melanocortins (e.g., adrenocorticotrophin, ACTH an...

The issue of which melanocortin receptor (MC-R) is responsible for the anti-inflammatory effects of melanocortin peptides is still a matter of debate. Here we have addressed this aspect using a dual pharmacological and genetic approach, taking advantage of the recent characterization of more selective agonists/antagonists at MC1 and MC3-R as well as of the existence of a naturally defective MC1...

BACKGROUND Cyclotides are useful scaffolds to stabilize bioactive peptides. RESULTS Four melanocortin analogues of kalata B1 were synthesized. One is a selective MC4R agonist. CONCLUSION The analogues retain the native kalata B1 scaffold and introduce a designed pharmacological activity, validating cyclotides as protein engineering scaffolds. SIGNIFICANCE A novel type of melanocortin agon...

The amygdala is rich in melanocortin 4 receptors. Because the reduction in dietary fat intake after enterostatin is injected in the central nucleus of the amygdala (CeA) is blocked by a melanocortin 4 receptor antagonist, we investigated the role of melanocortin activity in the CeA in regulating food intake and macronutrient choice. Sprague-Dawley rats, fitted with CeA cannulas, were fed either...

Metz, Juriaan R., Edwin J. W. Geven, Erwin H. van den Burg, and Gert Flik. ACTH, -MSH, and control of cortisol release: cloning, sequencing, and functional expression of the melanocortin-2 and melanocortin-5 receptor in Cyprinus carpio. Am J Physiol Regul Integr Comp Physiol 289: R814–R826, 2005. First published May 12, 2005; doi:10.1152/ajpregu.00826.2004.—Cortisol release from fish head kidne...

To examine the role of the brain stem melanocortin system in long-term energy regulation, we assessed the effects of overproduction of proopiomelanocortin (POMC) in the caudal brain stem of F344xBN rats with adult-onset obesity. Recombinant adeno-associated viral vector encoding POMC gene was delivered to the nucleus of solitary tract (NTS) in the hindbrain, and food intake, body weight, glucos...

Obesity results from a synergistic relationship between genes and the environment. The phenotypic expression of genetic factors involved in obesity is variable, allowing to distinguish several clinical pictures of obesity. Monogenic obesity is described as rare and severe early-onset obesity with abnormal feeding behavior and endocrine disorders. This is mainly due to autosomal recessive mutati...