SVK14 cells express an MCH binding site different from the MCH1 or MCH2 receptor

Audinot, Valérie; Lahaye, Chantal; Suply, Thomas; Rovère, Carole; Rodriguez, Marianne; Nicolas, Jean Paul; Beauverger, Philippe; Cardinaud, Bruno; Galizzi, J P; Fauchere, Jean Luc; Nahon, Jean‐Louis; Boutin, Jean A.

doi:10.1016/s0006-291x(02)00763-5

Cited by 10 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of an MCH analog named [Phe 13 , Tyr 19 ]-MCH permitted the discovery of binding sites on various mammalian cells lines including melanoma cells [129] and SVK-14 keratinocyte cells [130]. However, using this analog, the low reliability of binding properties and of intracellular signaling associated with its binding, made the overt expression of functional MCH receptors in these cells highly questionable [131,132].…”

Section: A Functional Antagonist Of α-Msh: the Melanin-concentrating ...mentioning

confidence: 99%

The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis

Nahon

2006

Comptes Rendus. Biologies

Self Cite

106

View full text Add to dashboard Cite

A number of different neuropeptides exert powerful concerted controls on feeding behavior and energy balance, most of them being produced in hypothalamic neuronal networks under stimulation by anabolic and catabolic peripheral hormones such as ghrelin and leptin, respectively. These peptide-expressing neurons interconnect extensively to integrate the multiple opposing signals that mediate changes in energy expenditure. In the present review I have summarized our current knowledge about two key peptidic systems involved in regulating appetite and energy homeostasis, the melanocortin system (α-MSH, agouti and Agouti-related peptides, MC receptors and mahogany protein) and the melanin-concentrating hormone system (proMCH-derived peptides and MCH receptors) that contribute to satiety and feeding-initiation, respectively, with concurrent effects on energy expenditure. I have focused particularly on recent data concerning transgenic mice and the ongoing development of MC/MCH receptor antagonists/agonists that may represent promising drugs to treat human eating disorders on both sides of the energy balance (anorexia, obesity).

show abstract

Section: A Functional Antagonist Of α-Msh: the Melanin-concentrating ...mentioning

confidence: 99%

The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis

Nahon

2006

Comptes Rendus. Biologies

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…This polypeptide was thus renamed the MCH-1 receptor. A second MCH receptor (MCH-2 receptor) has also been identified (7)(8)(9)(10)(11), and there is some evidence of an MCH binding site that is distinct from these two receptors (12).…”

mentioning

confidence: 99%

Periplakin Interferes with G Protein Activation by the Melanin-concentrating Hormone Receptor-1 by Binding to the Proximal Segment of the Receptor C-terminal Tail

Murdoch

Feng

Bächner

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

The orexigenic cyclic 19 amino acid peptide melanin-concentrating hormone (MCH) 1 (1) is the natural ligand for the G protein-coupled receptor (GPCR) originally designated SLC-1 (also called GPR24 in some studies) because of its relatedness to the receptors for somatostatin (2-6). This polypeptide was thus renamed the MCH-1 receptor. A second MCH receptor (MCH-2 receptor) has also been identified (7-11), and there is some evidence of an MCH binding site that is distinct from these two receptors (12).Even before identification of the MCH receptors a clear role for MCH in feeding and energy balance and homeostasis had been established (1). A solid body of genetic and pharmacological evidence now supports a role for MCH and the MCH-1 receptor in the modulation of food intake and energy expenditure. Key data derive from the genetic ablation of both MCH (13) and the MCH-1 receptor (14, 15) in mice. These alterations produced animals that were both lean and resistant to dietinduced obesity. Mice lacking the MCH-1 receptor have been reported to be hyperphagic (14, 15) but to be both hyperactive and to have altered metabolism, and this may explain the apparent paradox of being resistant to obesity but eating more. Studies also indicate that acute and chronic administration of MCH enhances food intake and body weight (16) and that overexpression of MCH in transgenic mice leads to obesity and insulin resistance (17). A role for the MCH-2 receptor in these effects is unlikely because genetic evidence indicates that mice do not express a functional form of this receptor (18). Furthermore, the distribution of the MCH-1 receptor in the central nervous system (19) also suggests that antagonists at the MCH-1 receptor might provide a treatment for obesity (for review, see Refs. 20 and 21). High throughput screening efforts have led to the identification of small molecule MCH-1 receptor antagonists with diverse structural features and drug-like properties. In vivo results with two of these antagonists indicate efficacy in several animal models of body weight regulation and feeding behavior (21). At least when expressed in

show abstract

“…These cells do not express mRNAs corresponding to MCH1R and MCH2R, but still possess a specific binding site for an MCH analog (Drozdz et al, '95;Eberle et al, 2004). The binding site characterized in the human SVK14 cell line differs from MCH1R and MCH2R, since it is not associated with a classical GPCR transduction pathway (Audinot et al, 2002). On the other hand, a photocrosslinking study with a biologically active photo radioligand revealed the presence of a specifically labeled band bound to mouse melanoma cells (Eberle et al, 2004).…”

Section: Identification Of Mch Receptorsmentioning

confidence: 99%

Identification of melanin‐concentrating hormone receptor and its impact on drug discovery

Saito

Maruyama

2006

J. Exp. Zool.

View full text Add to dashboard Cite

The neuropeptide melanin-concentrating hormone (MCH) was originally isolated from the pituitary of salmon, in which it causes skin paling. MCH is also found abundantly in mammalian neurons, and has been detected in the lateral hypothalamus and zona incerta, brain regions that are at the center of feeding behavior. Acute central administration of MCH leads to a rapid and significant increase in food intake, while MCH expression changes in states of altered energy balance, such as fasting and obesity. Furthermore, MCH knockout mice tend toward hypophagia and leanness. In 1999, we and four other groups identified an orphan G-protein-coupled receptor (GPCR) as a specific receptor for MCH (MCH-1 receptor). Although a second MCH receptor (MCH-2 receptor) was isolated in humans, it was found to be non-functional or encode a non-functional pseudogene in non-human species, including rodents. The discovery of these MCH receptors permitted the launch of a broad array of drug screening efforts and three MCH-1 receptor antagonists were identified to reduce food intake and body weight. Interestingly, some antagonists unexpectedly produced evidence that blockade of these receptors has antidepressant and anxiolytic activities. The expressions of the MCH receptors, which have been implicated in regulating emotion, stress and motivation, make MCH an excellent candidate for integrating the various homeostatic stimuli necessary for maintaining the proper conditions of energy metabolism and other physiological functions. Finally, the speed at which MCH receptor studies have been undertaken exemplifies the impact that this deorphanized GPCR will have on setting the stage for more detailed physiological studies.

show abstract

SVK14 cells express an MCH binding site different from the MCH1 or MCH2 receptor

Cited by 10 publications

References 48 publications

The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis

The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis

Periplakin Interferes with G Protein Activation by the Melanin-concentrating Hormone Receptor-1 by Binding to the Proximal Segment of the Receptor C-terminal Tail

Identification of melanin‐concentrating hormone receptor and its impact on drug discovery

Contact Info

Product

Resources

About