Search results for "Melanocortin 4 receptor"

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Functional Evaluation of THIQ, a Melanocortin 4 Receptor Agonist, in Models of Food Intake and Inflammation

2007

The central melanocortinergic system plays an important role in regulating different aspects of energy homeostasis and the immunomodulatory response. In the present study, we evaluated the in vivo activities of food intake suppression and anti-inflammatory activity of THIQ, which has been proposed to possess high and selective melanocortin-4 receptor agonistic activity in vitro. The results showed that THIQ (0.1, 0.3 and 1 nmol/rat, intracerebroventricularly) is less effective in reducing food intake and body weights of rats than the non-selective melanocortin receptor agonist melanotan II. Electron paramagnetic resonance measurements in mice brain tissue showed that THIQ at doses of 0.001 …

LipopolysaccharidesMaleAgonistmedicine.medical_specialtymedicine.drug_classAnti-Inflammatory AgentsBiologyNitric OxideToxicologyPeptides CyclicEnergy homeostasisEatingMiceMelanocortin receptorIn vivoTetrahydroisoquinolinesInternal medicinemedicineAnimalsRats WistarReceptorInjections IntraventricularInflammationPharmacologyMice Inbred ICRDose-Response Relationship DrugBody Weightdigestive oral and skin physiologyElectron Spin Resonance SpectroscopyBrainMelanotan IIGeneral MedicineTriazolesRatsMelanocortin 4 receptorDisease Models AnimalEndocrinologyalpha-MSHTHIQReceptor Melanocortin Type 4medicine.drugBasic & Clinical Pharmacology & Toxicology
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High affinity agonistic metal ion binding sites within the melanocortin 4 receptor illustrate conformational change of transmembrane region 3.

2003

We created a molecular model of the human melanocortin 4 receptor (MC4R) and introduced a series of His residues into the receptor protein to form metal ion binding sites. We were able to insert micromolar affinity binding sites for zinc between transmembrane region (TM) 2 and TM3 where the metal ion alone was able to activate this peptide binding G-protein-coupled receptor. The exact conformation of the metal ion interactions allowed us to predict the orientation of the helices, and remodeling of the receptor protein indicated that Glu100 and Ile104 in TM2 and Asp122 and Ile125 in TM3 are directed toward a putative area of activation of the receptor. The molecular model suggests that a rot…

Protein ConformationAmino Acid MotifsPeptide bindingPlasma protein bindingTransfectionBiochemistryCell LineReceptors G-Protein-CoupledProtein structureCyclic AMPHumansPoint MutationBinding siteReceptorMolecular BiologyBinding SitesChemistryMembrane ProteinsCell BiologyMelanocortin 4 receptorCytosolic partZincBiochemistryBiophysicsReceptor Melanocortin Type 4MelanocortinProtein BindingThe Journal of biological chemistry
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