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https://www.readbyqxmd.com/read/28540228/research-in-pharmacotherapy-for-erectile-dysfunction
#1
REVIEW
Ji-Kan Ryu, Jun-Kyu Suh, Arthur L Burnett
Although oral phosphodiesterase-5 (PDE5) inhibitors are generally accepted as an effective therapy for erectile dysfunction (ED), men with ED from diabetes or radical prostatectomy respond poorly to these drugs. Many researchers have tried to develop novel therapeutics that target alternative molecular pathways. A group of therapeutics belongs to centrally acting agents that target dopamine and melanocortin receptors. The other one is the peripherally acting agents that target soluble guanylate cyclase, Rho-kinase pathway, and Maxi-K channel, etc...
April 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28520814/rs12970134-near-mc4r-is-associated-with-appetite-and-beverage-intake-in-overweight-and-obese-children-a-family-based-association-study-in-chinese-population
#2
Shuo Wang, Jieyun Song, Yide Yang, Nitesh V Chawla, Jun Ma, Haijun Wang
BACKGROUND: Recent studies indicated that eating behaviors are under genetic influence, and the melanocortin 4 receptor (MC4R) gene polymorphisms can affect the total energy intake and the consumption of fat, protein and carbohydrates. Our study aims at investigating the association of the MC4R polymorphism with appetite and food intake among Chinese children. METHODS: A family-based association study was conducted among 151 Chinese trios whose offsprings were overweight/obese children aged 9-15 years...
2017: PloS One
https://www.readbyqxmd.com/read/28512117/the-interaction-of-mc3r-and-mc4r-with-mrap2-acth-%C3%AE-msh-and-agrp-in-chickens
#3
Jiannan Zhang, Xin Li, Yawei Zhou, Lin Cui, Jing Li, Chenlei Wu, Yiping Wan, Juan Li, Yajun Wang
The interaction of melanocortin-4 (MC4R) and melanocortin-3 (MC3R) receptors with proopiomelanocortin (POMC)-derived peptides (e.g. α-MSH), agouti-related protein (AgRP), and melanocortin-2 receptor accessory protein 2 (MRAP2) is suggested to play critical roles in energy balance of vertebrates. However, evidence on their interaction in birds remains scarce. Our study aims to reveal their interaction in chickens and the results showed that: 1) chicken (c-)MC3R and cMC4R expressed in CHO cells can be activated by α-MSH and ACTH1-39 equipotently, monitored by a pGL3-CRE-luciferase reporter system; 2) cMC3R and cMC4R, when co-expressed with cMRAP2 (or cMRAP, a cMRAP2 homolog), show increased sensitivity to ACTH treatment and thus likely act as ACTH-preferring receptors, and the interaction between cMC3R/cMC4R and cMRAP2 was demonstrated by co-immunoprecipitation assay; 3) both cMC3R and cMC4R display constitutive activity when expressed in CHO cells, as monitored by Dual-luciferase reporter assay, and cMRAP2 (and cMRAP) can modulate their constitutive activity; 4) AgRP inhibits the constitutive activity of cMC3R/cMC4R, and it also antagonizes ACTH/α-MSH action on cMC4R/cMC3R, indicating that AgRP functions as the inverse agonist and antagonist for both receptors...
May 16, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#4
K Kaineder, T Birngruber, G Rauter, B Obermüller, J Eichler, J Münzker, W Al-Zoughbi, S I Mautner, S S Torekov, B Hartmann, P Kotzbeck, T R Pieber
BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity treatment where it induces body weight reduction possibly via the hypothalamus, which regulates energy homeostasis. In animal studies, acute liraglutide treatment triggers satiety, weight loss and activates thermogenesis in adipose tissue. However, the precise mechanisms how liraglutide affects in particular chronic weight loss are still under investigation. OBJECTIVES: We aimed to evaluate whether chronic hypothalamic or chronic subcutaneous administration of liraglutide induces sustained weight loss through altered adipose tissue function and to what extent hypothalamic neuronal appetite regulators are involved in the liraglutide-induced weight loss in healthy lean rats on a normal diet...
April 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#5
Long The Nguyen, Sonia Saad, Yi Tan, Carol Pollock, Hui Chen
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect.  In this study, we show that offspring born to HFD-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28499989/melanocortin-receptor-accessory-proteins-mraps-functions-in-the-melanocortin-system-and-beyond
#6
REVIEW
Alix A J Rouault, Dinesh K Srinivasan, Terry C Yin, Abigail A Lee, Julien A Sebag
G-protein coupled receptors (GPCRs) are regulated by numerous proteins including kinases, G-proteins, β-arrestins and accessory proteins. Several families of GPCR accessory proteins like Receptor Activity Modifying Proteins, Receptor Transporting Proteins and Melanocortin Receptor Accessory Proteins (MRAPs) have been identified as regulator of receptor trafficking, signaling and ligand specificity. The MRAP family contains two members, MRAP1 and MRAP2, responsible for the formation of a functional ACTH receptor and for the regulation of energy homeostasis respectively...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28499988/melanocortin-neurons-multiple-routes-to-regulation-of-metabolism
#7
REVIEW
Wen-Jie Shen, Ting Yao, Xingxing Kong, Kevin W Williams, Tiemin Liu
The burden of disability, premature death, escalating health care costs and lost economic productivity due to obesity and its associated complications including hypertension, stroke, cardiovascular disease and type 2 diabetes is staggering [1, 2]. A better understanding of metabolic homeostatic pathways will provide us with insights into the biological mechanisms of obesity and how to fundamentally address this epidemic [3-6]. In mammals, energy balance is maintained via a homeostatic system involving both peripheral and central melanocortin systems; changes in body weight reflect an unbalance of the energetic state [7-9]...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28495271/the-melanocortin-2-receptor-of-the-rainbow-trout-identifying-a-role-for-critical-positions-in-transmembrane-domain-4-extracellular-loop-2-and-transmembrane-domain-5-in-the-activation-of-rainbow-trout-mc2r
#8
Liang Liang, Perry V Davis, Michael R Dores, Robert M Dores
The activation of either teleost or tetrapod melanocortin-2 receptor (MC2R) orthologs requires interaction between the HFRW motif and R/KKRRP motif in the primary sequence of ACTH, and two corresponding sites on the melanocortin 2 receptor. While the HFRW contact site on MC2R appears to involve residues in TM2, TM3, and TM6, several studies on human MC2R point to the EC2/TM5 region of MC2R as a possible location for the R/KKRRP contact site. In this study nineteen single-alanine mutants of rainbow trout (rt) MC2R were made beginning at V(153) in TM4, at all positions in EC2 (extracellular loop 2), to F(175) in TM5...
May 8, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28491052/receptor-mediated-melanoma-targeting-with-radiolabeled-%C3%AE-melanocyte-stimulating-hormone-relevance-of-the-net-charge-of-the-ligand
#9
Jean-Philippe Bapst, Alex N Eberle
A majority of melanotic and amelanotic melanomas overexpress melanocortin type 1 receptors (MC1Rs) for α-melanocyte-stimulating hormone. Radiolabeled linear or cyclic analogs of α-MSH have a great potential as diagnostic or therapeutic tools for the management of malignant melanoma. Compounds such as [(111)In]DOTA-NAP-amide exhibit high affinity for the MC1R in vitro, good tumor uptake in vivo, but they may suffer from relatively high kidney uptake and retention in vivo. We have shown previously that the introduction of negative charges into radiolabeled DOTA-NAP-amide peptide analogs may enhance their excretion and reduce kidney retention...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28486572/evaluation-of-mc1r-high-throughput-nucleotide-sequencing-data-generated-by-the-1000-genomes-project
#10
Leonardo Arduino Marano, Letícia Marcorin, Erick da Cruz Castelli, Celso Teixeira Mendes-Junior
The advent of next-generation sequencing allows simultaneous processing of several genomic regions/individuals, increasing the availability and accuracy of whole-genome data. However, these new approaches may present some errors and bias due to alignment, genotype calling, and imputation methods. Despite these flaws, data obtained by next-generation sequencing can be valuable for population and evolutionary studies of specific genes, such as genes related to how pigmentation evolved among populations, one of the main topics in human evolutionary biology...
May 8, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28484396/nesfatin-1-in-the-lateral-parabrachial-nucleus-inhibits-food-intake-modulates-excitability-of-glucosensing-neurons-and-enhances-ucp1-expression-in-brown-adipose-tissue
#11
Jun-Hua Yuan, Xi Chen, Jing Dong, Di Zhang, Kun Song, Yue Zhang, Guang-Bo Wu, Xi-Hao Hu, Zheng-Yao Jiang, Peng Chen
Nesfatin-1, an 82-amino acid neuropeptide, has been shown to induce anorexia and energy expenditure. Food intake is decreased in ad libitum-fed rats following injections of nesfatin-1 into the lateral, third, or fourth ventricles of the brain. Although the lateral parabrachial nucleus (LPBN) is a key regulator of feeding behavior and thermogenesis, the role of nesfatin-1 in this structure has not yet been delineated. We found that intra-LPBN microinjections of nesfatin-1 significantly reduced nocturnal cumulative food intake and average meal sizes without affecting meal numbers in rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28453643/early-onset-obesity-unrecognized-first-evidence-for-gnas-mutations-and-methylation-changes
#12
Annette Grüters-Kieslich, Monica Reyes, Amita Sharma, Cem Demirci, Terry J DeClue, Erwin Lankes, Dov Tiosano, Dirk Schnabel, Harald Jüppner
Context: Early-onset obesity, characteristic for disorders affecting the leptin-melanocortin pathway, is also observed in pseudohypoparathyroidism type Ia (PHP1A), a disorder caused by maternal GNAS mutations that disrupt expression or function of the stimulatory G protein (Gsα). Mutations and/or epigenetic abnormalities at the same genetic locus are also the cause of pseudohypoparathyroidism type Ib (PHP1B). However, although equivalent biochemical and radiographic findings can be encountered in these related disorders caused by GNAS abnormalities they are considered distinct clinical entities...
April 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28453292/discovery-of-mixed-pharmacology-melanocortin-3-agonists-and-melanocortin-4-receptor-tetrapeptide-antagonist-compounds-tacos-based-on-the-sequence-ac-xaa-1-arg-pi-dphe-xaa-4-nh2
#13
Skye R Doering, Katie T Freeman, Sathya M Schnell, Erica M Haslach, Marvin Dirain, Ginamarie Debevec, Phaedra Geer, Radleigh G Santos, Marc A Giulianotti, Clemencia Pinilla, Jon R Appel, Robert C Speth, Richard A Houghten, Carrie Haskell-Luevano
The centrally expressed melanocortin-3 and -4 receptors (MC3R/MC4R) have been studied as possible targets for weight management therapies, with a preponderance of studies focusing on the MC4R. Herein, a novel tetrapeptide scaffold [Ac-Xaa(1)-Arg-(pI)DPhe-Xaa(4)-NH2] is reported. The scaffold was derived from results obtained from a MC3R mixture-based positional scanning campaign. From these results, a set of 48 tetrapeptides were designed and pharmacologically characterized at the mouse melanocortin-1, -3, -4, and -5 receptors...
May 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28452072/pgc-1%C3%AE-in-melanoma-a-key-factor-for-antioxidant-response-and-mitochondrial-function
#14
Margalida Torrens-Mas, Daniel González-Hedström, Marta Abrisqueta, Pilar Roca, Jordi Oliver, Jorge Sastre-Serra
Melanocortin 1 receptor (MC1R) and BRAF are common mutations in melanoma. Through different pathways, they each regulate the expression of PGC-1α, which is a key factor in the regulation of mitochondrial biogenesis and the antioxidant response. Our aim was to study the importance of the different regulatory characteristics of MC1R and BRAF on the pathways they regulate in melanoma. For this purpose, ROS production, levels of gene expression and enzymatic activities were analyzed in HBL and MeWo, with wild-type MC1R and BRAF, and A375 cells with mutant MC1R and BRAF...
April 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28450851/regulation-of-agouti-related-protein-and-pro-opiomelanocortin-gene-expression-in-the-avian-arcuate-nucleus
#15
REVIEW
Timothy Boswell, Ian C Dunn
The arcuate nucleus is generally conserved across vertebrate taxa in its neuroanatomy and neuropeptide expression. Gene expression of agouti-related protein (AGRP), neuropeptide Y (NPY), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) has been established in the arcuate nucleus of several bird species and co-localization demonstrated for AGRP and NPY. The proteins encoded by these genes exert comparable effects on food intake in birds after central administration to those seen in other vertebrates, with AGRP and NPY being orexigenic and CART and α-melanocyte-stimulating hormone anorexigenic...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28450348/melanocortin-1-receptor-signaling-regulates-cholesterol-transport-in-macrophages
#16
Petteri Rinne, Martina Rami, Salla L Nuutinen, Donato Santovito, Emiel P C van der Vorst, Raquel Guillamat-Prats, Leo-Pekka Lyytikäinen, Emma Raitoharju, Niku Oksala, Larisa Ring, Minying Cai, Victor J Hruby, Terho J Lehtimäki, Christian Weber, Sabine Steffens
Background -The melanocortin 1 receptor (MC1-R) is expressed by monocytes and macrophages, where it exerts anti-inflammatory actions upon stimulation with its natural ligand α-melanocyte-stimulating hormone (α-MSH). The present study was designed to investigate the specific role of MC1-R in the context of atherosclerosis and possible regulatory pathways of MC1-R beyond anti-inflammation. Methods -Human and mouse atherosclerotic samples and primary mouse macrophages were used to study the regulatory functions of MC1-R...
April 27, 2017: Circulation
https://www.readbyqxmd.com/read/28442450/implementing-an-internet-delivered-skin-cancer-genetic-testing-intervention-to-improve-sun-protection-behavior-in-a-diverse-population-protocol-for-a-randomized-controlled-trial
#17
Jennifer L Hay, Marianne Berwick, Kate Zielaskowski, Kirsten Am White, Vivian M Rodríguez, Erika Robers, Dolores D Guest, Andrew Sussman, Yvonne Talamantes, Matthew R Schwartz, Jennie Greb, Jessica Bigney, Kimberly A Kaphingst, Keith Hunley, David B Buller
BACKGROUND: Limited translational genomic research currently exists to guide the availability, comprehension, and appropriate use of personalized genomics in diverse general population subgroups. Melanoma skin cancers are preventable, curable, common in the general population, and disproportionately increasing in Hispanics. OBJECTIVE: Variants in the melanocortin-1 receptor (MC1R) gene are present in approximately 50% of the population, are major factors in determining sun sensitivity, and confer a 2-to-3-fold increase in melanoma risk in the general population, even in populations with darker skin...
April 25, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28438719/chick-subcutaneous-and-abdominal-adipose-tissue-depots-respond-differently-in-lipolytic-and-adipogenic-activity-to-%C3%AE-melanocyte-stimulating-hormone-%C3%AE-msh
#18
Steven L Shipp, Guoqing Wang, Mark A Cline, Elizabeth R Gilbert
In birds, α-MSH is anorexigenic, but effects on adipose tissue are unknown. Four day-old chicks were intraperitoneally injected with 0 (vehicle), 5, 10, or 50μg of α-MSH and subcutaneous and abdominal adipose tissue collected at 60min for RNA isolation (n=10). Plasma was collected post-euthanasia at 60 and 180min for measuring non-esterified fatty acids (NEFA) and α-MSH (n=10). Relative to the vehicle, food intake was reduced in the 50μg-treated group. Plasma NEFAs were greater in 10μg than vehicle-treated chicks at 3h...
July 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28434791/neuronal-cells-derived-from-human-induced-pluripotent-stem-cells-as-a-functional-tool-of-melanocortin-system
#19
Nobuko Yamada-Goto, Yukari Ochi, Goro Katsuura, Yui Yamashita, Ken Ebihara, Michio Noguchi, Junji Fujikura, Daisuke Taura, Masakatsu Sone, Kiminori Hosoda, Paul E Gottschall, Kazuwa Nakao
BACKGROUND: The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development. METHODS: In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed. RESULTS: The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1)...
April 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28433713/biased-signaling-at-neural-melanocortin-receptors-in-regulation-of-energy-homeostasis
#20
Li-Kun Yang, Ya-Xiong Tao
The global prevalence of obesity highlights the importance of understanding on regulation of energy homeostasis. The central melanocortin system is an important intersection connecting the neural pathways controlling satiety and energy expenditure to regulate energy homeostasis by sensing and integrating the signals of external stimuli. In this system, neural melanocortin receptors, melanocortin-3 and -4 receptors (MC3R and MC4R), play crucial roles in the regulation of energy homeostasis. Recently, multiple intracellular signaling pathways and biased signaling at neural MCRs have been discovered, providing new insights into neural MCR signaling...
April 19, 2017: Biochimica et Biophysica Acta
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