Disease relevance of MCHR2

• We show here that the human melanoma cell line SK-MEL-37 expresses SLC-1 mRNA but not MCHR2 by RT-PCR analysis and immunofluorescence studies [1].
• Northern blot and in situ hybridization analysis of human and monkey tissue shows that expression of MCH-2R mRNA is restricted to several regions of the brain, including the arcuate nucleus and the ventral medial hypothalamus, areas implicated in regulation of body weight [2].
• Because of the ease of administration, rapid reversibility of effects, and lower AUC of serum T levels achieved compared to those of TE injections, SLT may be especially suitable for treatment of boys with delayed puberty and older men with androgen deficiency [3].
• SLT presents an interesting concept to alleviate the organ shortage for children with end-stage liver disease [4].
• SLT toxicity depends on entry into the target cell via its host cell glycolipid receptor, globotriaosylceramide (Gb3) [5].

Psychiatry related information on MCHR2

• Theory (SLT), which addresses both the psychosocial dynamics underlying health behavior and the methods of promoting behavior change, while emphasizing cognitive processes and their effect on behavior [6].
• This was shown to hold more promise than the SLT in discriminating between dementia and depression [7].

High impact information on MCHR2

• Why mice have lost genes for COL21A1, STK17A, GPR145 and AHRI: evidence for gene deletion at evolutionary breakpoints in the rodent lineage [8].
• In contrast to MCHR1, which is intronless in the coding region and is located at the chromosomal locus 22q13.3, the MCHR2 gene has multiple exons and is mapped to locus 6q21 [9].
• MCHR2 is specifically activated by nanomolar concentrations of MCH, binds to MCH with high affinity, and signals through Gq protein [9].
• In addition, the human MCH-2R gene was mapped to the long arm of chromosome 6 at band 6q16.2-16.3, a region reported to be associated with cytogenetic abnormalities of obese patients [2].
• MCH-2R displayed high-affinity MCH binding, resulting in inositol phosphate turnover and release of intracellular calcium in mammalian cells [2].

Chemical compound and disease context of MCHR2

• AIM: To compare 90 degrees , 180 degrees , and 360 degrees selective laser trabeculoplasty (SLT, 532 nm Nd:YAG laser) with latanoprost 0.005% for the control of intraocular pressure (IOP) in ocular hypertension (OHT) and open angle glaucoma (OAG) [10].
• Fecal samples from slaughtered cattle were studied for enterohaemorrhagic Escherichia coli (EHEC) by DNA hybridization with biotin-labelled DNA probes specific for the EHEC virulence plasmid, Shiga-like toxin I (SLT I), Shiga-like toxin II (SLT II) and eae gene [11].

Biological context of MCHR2

• In conclusion, the binding site characterized in the SVK14 cell line is distinct from the MCH1 and MCH2 receptors and deserves therefore further investigation [12].
• Quantitative polymerase chain reaction analysis of the SLT gene expression in human tissues showed that the SLT receptor is expressed mainly in brain areas including the cerebral cortex, amygdala, hippocampus, and corpus callosum, as well as in a limited number of peripheral tissues [13].
• Here we show that several non-human species (rat, mouse, hamster, guinea pig, and rabbit) do not have functional MCHR2 receptors, or encode a nonfunctional MCHR2 pseudogene while retaining GPR24 expression [14].
• The phylogenetic analysis shows that these are orthologues to the mammalian MCH-R1 and MCH-R2 showing 49 and 30% amino acid sequence identity to the corresponding human receptors while they have 31% amino acid sequence identify between them [15].
• MCH-R1 has one intron in the extracellular N-terminal region and MCH-R2 has one intron in the DRY motif, which is a homologous position to one of the five introns of human MCH-R2 [15].

Anatomical context of MCHR2

• DNA constructs containing MCH-R1 and MCH-R2 SNPs were generated and expressed in CHO cells [16].
• In this MicroReview, we will briefly summarize recent progress in Shiga toxin- and SLT-related research and present evidence supporting the concept that these toxins contribute to pathogenesis by directly damaging vascular endothelial cells, thereby disrupting the homeostatic properties of these cells [17].
• Mean pulmonary artery pressures fell from 55 +/- 6 mm Hg before SLT to 21 +/- 3 mm Hg after SLT; p less than 0.001 [18].
• Seventy-six percent (26 of 34) of E. coli isolates that hybridized with the SLT II probe were cytotoxic to Vero but not to HeLa cells, suggesting that they produced the variant of SLT II [19].
• To investigate possible changes following lung transplantation, the structure and in vitro ciliary beat frequency (CBF) of airway epithelium from the cytology brushings of 9 heart-lung (HLT) and 5 single-lung (SLT) transplant recipients were examined [20].

Associations of MCHR2 with chemical compounds

• For example, peptide 26 with d-Arg in place of L-Arg in position 6 and Asn in place of Gly in position 10, Ac-dArg(6)-cyclo(S-S)(Cys(7)-Met(8)-Leu(9)-Asn(10)-Arg(11)-Val(12)-Tyr(13)-Arg(14)-Pro(15)-Cys(16))-NH(2), was a potent hMCH-1R agonist (IC(50) = 0.5 nm, EC(50) = 47 nm) with more than 200-fold selectivity with respect to hMCH-2R [21].
• Similarly, serum sex hormone-binding globulin levels showed significant decreases with androgen replacement only in the TE and SLT 5.0 mg range groups [3].
• After SLT administration, serum testosterone (T) levels peaked at 20 min and then fell, reaching baseline levels by 360 min [3].
• SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001) [22].
• The central role of SLT in the virulence of the O91:H21 EHEC strains was supported by the finding that streptomycin-treated mice preinoculated with monoclonal antibody specific for SLT-II survived oral challenge with either B2F1 (Strr) or H414-36/89 (Strr) [23].

Physical interactions of MCHR2

• Labeled Ala17 MCH had little demonstrable binding affinity for MCHR2 [24].

Regulatory relationships of MCHR2

• DISCUSSION: These data indicate that potential therapeutics designed to act at the MCH receptor are unlikely to have altered effects in subpopulations that express variant forms of MCH-R1 or MCH-R2 [16].

Other interactions of MCHR2

• Herein we identify and characterize a novel receptor for human MCH (MCH-R2) [25].

Analytical, diagnostic and therapeutic context of MCHR2

• We cloned and functionally characterized dog, ferret, and rhesus GPR24 and MCHR2 in mammalian cells and studied their brain distribution patterns by in situ hybridization [14].
• Molecular cloning and functional characterization of MCH2, a novel human MCH receptor [26].
• We conclude that SLT may be a useful addition to the currently available injectable and transdermal delivery systems for treatment of hypogonadal men [3].
• Continuous peritoneal infusion of Shiga-like toxin II (SLT II) as a model for SLT II-induced diseases [27].
• BACKGROUND/AIMS: This study aims to compare the results of living donor (LDLT), cadaveric split (SLT) and domino (DO) liver transplantation which are currently available alternatives to the conventional cadaveric full-size liver transplantation (CAD) [28].

References