Similarities in cellular expression and functions of melanin-concentrating hormone and atrial natriuretic factor in the rat digestive tract.

Hervieu, Guillaume; Volant, Karine; Гришина, О. В.; Descroix-Vagne, M.; Nahon, Jean‐Louis

doi:10.1210/endo.137.2.8593803

Cited by 39 publications

(22 citation statements)

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“…In the gut, likely sources of MCH are the enteric nervous system, enterochromaffin cells, and resident or infiltrating immune cells, based on evidence described here (Fig. 4) and in previous reports (10,(12)(13)(14)42).…”

Section: Discussionsupporting

confidence: 64%

Melanin-concentrating hormone as a mediator of intestinal inflammation

Kokkotou¹,

Moss²,

Torres³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Melanin-concentrating hormone (MCH) is expressed primarily in the hypothalamus and has a positive impact on feeding behavior and energy balance. Although MCH is expressed in the gastrointestinal tract, its role in this system remains elusive. We demonstrate that, compared to wild type, mice genetically deficient in MCH had substantially reduced local inflammatory responses in a mouse model of experimental colitis induced by intracolonic administration of 2,4,6 trinitrobenzene sulfonic acid (TNBS). Likewise, mice receiving treatments with an anti-MCH antibody, either prophylactically or after the establishment of colitis, developed attenuated TNBS-associated colonic inflammation and survived longer. Consistent with a potential role of MCH in intestinal pathology, we detected increased colonic expression of MCH and its receptor in patients with inflammatory bowel disease. Moreover, we found that human colonic epithelial cells express functional MCH receptors, the activation of which induces IL-8 expression. Taken together, these results clearly implicate MCH in inflammatory processes in the intestine and perhaps elsewhere.experimental colitis ͉ IL-8 ͉ inflammatory bowel disease ͉ neuropeptides ͉ MCH deficient mice M elanin-concentrating hormone (MCH) is a 17-to 19-aa cyclic neuropeptide conserved from fish to human (1) and predominantly localized in the brain (2). Several pharmacological and genetic studies revealed a role for this peptide in the regulation of feeding behavior and energy expenditure toward a positive energy balance (3-5). More recent studies extended the physiological functions of MCH as a broad regulator of cognitive and autonomic aspects related to rewarding behaviors (6, 7). Outside the brain, MCH is localized in the pancreas (8), skin (9), and gastrointestinal tract (10). It has been also found in tissular and circulating immune cells (11)(12)(13)(14). However, the physiological role of MCH in these peripheral tissues has yet to be established.In humans, two G-protein-coupled receptors for MCH have been identified, MCHR1 (also known as SLC1 or GPR24) (15-18) and MCHR2 (19-21), whereas rodents express only MCHR1. In the rodent brain, MCHR1 is expressed in areas important for feeding, learning and motivated behavior, integration of sensory and gustatory inputs, autonomic control, and arousal (22, 23). MCHR1 mRNA is also expressed in the thyroid, kidney, adipose tissue, lung, testes, and tongue (23), whereas functional MCHR1 is also present in lymphocytes (12,14), insulin-producing cell lines (24), and mouse and human pancreatic islets (8).Several neuropeptides that are part of the neuroendocrine system exhibit important immunomodulatory effects and mediate inflammation in various organs, including the intestine (25, 26). There is little evidence to indicate expression of MCHR of either type in the intestine of animals or humans, and the role of MCH in inflammatory responses in the gut or elsewhere has not been evaluated. Based on these considerations and because MCH is also expressed in immune c...

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Section: Discussionsupporting

confidence: 64%

Melanin-concentrating hormone as a mediator of intestinal inflammation

Kokkotou¹,

Moss²,

Torres³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Other physiological roles of MCH include regulation of the hypothalamopituitary adrenal gland axis (11), modulation of water and electrolyte fluxes in the gut (12), stimulation of oxytocin secretion from isolated rat neurohypophysis (13), regulation of sensory processing (14), and modulation of monoaminergic activity in the medial preoptic area (15). In addition, several lines of evidence also suggest a role for MCH in modification of memory retention (16), modulation of other hormones regulating food intake (17) and sexual behavior (18) and involvement in seizure (19).…”

Section: Melanin-concentrating Hormone (Mch)mentioning

confidence: 99%

Identification and Pharmacological Characterization of a Novel Human Melanin-concentrating Hormone Receptor, MCH-R2

Wang¹,

Behan²,

O’Neill³

et al. 2001

Journal of Biological Chemistry

101

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Melanin-concentrating hormone (MCH) is a neuropeptide highly expressed in the brain that regulates several physiological functions mediated by receptors in the G protein-coupled receptor family. Recently an orphan receptor, SLC-1, has been identified as an MCH receptor (MCH-R1). Herein we identify and characterize a novel receptor for human MCH (MCH-R2Melanin-concentrating hormone (MCH) 1 is a cyclic neuropeptide originally identified in salmon pituitaries responsible for skin color changes in teleost fish (1). This peptide is composed of 17 amino acids (DTMRCMVGRVYRPCWEV), whereas the mammalian form of MCH is a 19-amino acid peptide (DFDMLRCMLGRVYRPCWQV) expressed throughout the brain with the highest concentration in the lateral hypothalamic and zona incerta areas (2-4).MCH plays a role in several important physiologic processes.The most active area of research on MCH has focused on the role of MCH in the regulation of feeding behavior and energy balance. Several studies provide evidence for a role for MCH in regulation of body weight.1) Mice that lack MCH are hypophagic and exhibit an increased metabolic rate, resulting in decreased body weight and body fat content (5). 2) Intracerebroventricular injection of MCH increases feeding in rats (6 -8).3) MCH, like several other appetite-regulating neuropeptides, is regulated by leptin in the hypothalamus (9, 10).Other physiological roles of MCH include regulation of the hypothalamopituitary adrenal gland axis (11), modulation of water and electrolyte fluxes in the gut (12), stimulation of oxytocin secretion from isolated rat neurohypophysis (13), regulation of sensory processing (14), and modulation of monoaminergic activity in the medial preoptic area (15). In addition, several lines of evidence also suggest a role for MCH in modification of memory retention (16), modulation of other hormones regulating food intake (17) and sexual behavior (18) and involvement in seizure (19). MCH is also localized in neurons functionally involved in circuits of the extrapyramidal motor systems from striatal centers to the thalamus and cerebral cortex and to the midbrain and spinal cord (20). The complex central nervous system expression pattern of MCH together with the many diverse functions mediated by MCH suggest the existence of more than one MCH receptor.The molecular identities of MCH receptors were unknown until recent reports of the first MCH receptor (MCH-R1) (21-25). MCH-R1 is composed of seven transmembrane domains typical of G protein-coupled receptors and binds to MCH with high affinity. MCH-R1 is coupled to G i , G o , and G q -type G proteins and mediates decreases in intracellular cAMP and increases in intracellular Ca 2ϩ levels, inositol phosphate production, and mitogen-activate protein kinase activity (26). In this report, we describe a novel MCH receptor identified through bioinformatic and molecular cloning approaches. The receptor is similar (35% identical) to the previously published MCH receptor, is able to bind 125 I-labeled MCH, and can be activated by ...

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“…Our own group has demonstrated MCH and MCHR1 immunoreactivity in the rat myenteric and submucosal plexus (24), whereas others have shown that vagal afferent neurons in both human and rat express MCH and its G protein-coupled seven-transmembrane receptor (MCHR1) (6). Moreover, when tested in an in situ ligated loop experiment, MCH stimulated Na ϩ and K ϩ fluxes in proximal colon; water, as well as Na ϩ and K ϩ fluxes in duodenum; and bicarbonate absorption in the jejunum (20).…”

mentioning

confidence: 99%