Disease relevance of Mchr1

• INTRODUCTION: Melanin concentrating hormone is an orexigenic hypothalamic neuropeptide, which plays an important role in the complex regulation of energy balance and body weight mediated by the melanin concentrating hormone receptor subtype 1 (MCH1) [1].
• These data show that the majority of dorsal root ganglion neurons exhibit somatostatin receptor-like IR thus suggesting a high potential for inhibition by somatostatin [2].
• We used real-time PCR to measure the hypothalamic expression of MCH and its receptor (MCHR1) in two contrasting models of altered nutritional status, namely, obesity induced by 8 weeks' voluntary overeating and food restriction for 10 days [3].

Psychiatry related information on Mchr1

• We have found high levels of expression of MCHR mRNA in most anatomical areas implicated in control of olfaction, with the exception of the main olfactory bulb [4].
• These data suggest that MCH and alpha-MSH exert opposing and antagonistic influences on feeding behavior and the stress response and may function in a coordinate manner to regulate metabolism through a novel mechanism mediated in part by an MCH receptor [5].

High impact information on Mchr1

• Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance [6].
• In fasted rats in which CB-1 and MCH-1 receptor expression was increased, administration of ghrelin prevented the downregulation by refeeding [6].
• Within the hypothalamus, MCHR mRNA was moderately expressed in the ventromedial nucleus, arcuate nucleus, and zona incerta, all of which serve key roles in the neuronal circuitry of feeding [4].
• Recently the orphan G protein-coupled receptor SLC-1 was identified as the MCH receptor (MCHR) [4].
• Preliminary analyses of MCHR mRNA distribution have supported a role for the MCH system in nutritional homeostasis [4].

Biological context of Mchr1

• The known high-affinity MCH1 receptor antagonist, SNAP-7941, exhibited an IC50 value of 1.66+/-0.10 nM that is very similar to the IC50 value of MCH in a radioligand binding assay with an excellent correlation coefficient (0.9884) [1].
• A repeat polymorphism of the form (CA)n was discovered in the 5'-untranslated region (UTR) of the gene and SLC-1 was mapped to chromosome 22, q13.3 [7].
• These data suggest that lipid peroxidation induces changes in membrane dynamics as detected by the fluorescent probes and such changes in membrane microviscosity may be the cause for alterations in Mch receptor kinetics [8].
• Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake [9].
• We conclude that MCH-1 receptor antagonism with T-226296 decreases food intake in DIO rats by selectively reducing meal size, and that the reduced food intake is not due to a generalized behavioral malaise [10].

Anatomical context of Mchr1

• Northern blot analysis revealed that SLC-1 is expressed in human brain regions, including the forebrain and hypothalamus [7].
• Expression of SLC-1 in COS-7 cells failed to show specific binding to radiolabelled Tyr1-somatostatin-14, naloxone, bremazocine, 1,3-di(2-tolyl)-guanidine (DTG), or haloperidol [7].
• We used in situ hybridization histochemistry and immunohistochemistry to determine the distribution of SLC-1 mRNA and its protein product in the rat brain and spinal cord [11].
• SLC-1 signals were observed in the cerebral cortex, caudate-putamen, hippocampal formation, amygdala, hypothalamus and thalamus, as well as in various nuclei of the mesencephalon and rhombencephalon [11].
• Effect of direct injection of melanin-concentrating hormone into the paraventricular nucleus: further evidence for a stimulatory role in the adrenal axis via SLC-1 [12].

Associations of Mchr1 with chemical compounds

• In addition, the MCH receptor (MCHR1) was coexpressed on about 50-55% of GnRH neurons [13].
• However, when membranes prepared from control caudate nuclei were incubated with thallium (1-100 microM) in vitro, we observed a dose-dependent decrease in DA and MCh receptor binding [14].
• Synthesis and structure-activity relationships of biarylcarboxamide bis-aminopyrrolidine urea derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1) [15].

Physical interactions of Mchr1

• A comparison with immunohistochemical staining using antisera against somatostatin receptor sequences revealed that the marked binding in laminae I-III coincided with the presence of somatostatin receptor-like immunoreactivity for the receptor subtypes 1, 2 and 3 [16].

Regulatory relationships of Mchr1

• The possibility that MCH and MCHR1 expression are positively regulated by leptin and insulin, which normally inhibit feeding, is a putative explanation for how appetite for palatable food is able to override mechanisms that prevent the development of obesity [3].

Other interactions of Mchr1

• Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1) [17].
• There were significant positive correlations (p<0.05) between plasma leptin concentration and both MCH and MCHR1 mRNA levels, and between plasma insulin and MCHR1 expression [3].
• Additionally, MCH was found to increase corticotropin-releasing factor (CRF) release from hypothalamic explants, and this effect was abolished by the specific SLC-1 antagonist SB-568849 [12].

Analytical, diagnostic and therapeutic context of Mchr1

• The performance of new vacuum filtration system was evaluated with MCH1 receptor binding assay and ligand washout experiments [18].
• In this experiment, we measured the expressions of MCH as well as of its receptor (SLC-1) in the hypothalamus of obese hyperphagic and lean Zucker rats by quantitative real time RT-PCR [19].

References