Tao Ya-Xiong, Huang Hui, Wang Zhi-Qiang, Yang Fan, Williams Jessica N, Nikiforovich Gregory V
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
Methods Enzymol. 2010;484:267-79. doi: 10.1016/B978-0-12-381298-8.00014-9.
The two neural melanocortin receptors (MCRs), melanocortin-3 and -4 receptors (MC3R and MC4R), are G protein-coupled receptors expressed primarily in the brain that regulate different aspects of energy homeostasis. The MCRs are unique in having endogenous antagonists, agouti and agouti-related protein (AgRP). These antagonists were later shown to be inverse agonists. The MC3R has little or no constitutive activity, whereas the MC4R has significant constitutive activity that can easily be detected. We describe herein methods for detecting constitutive activities in these receptors and small molecule ligands as inverse agonists. AgRP is an inverse agonist for both MC3R and MC4R. We also provide models for the constitutively active MC4R mutants.
两种神经黑素皮质素受体（MCRs），即黑素皮质素-3和-4受体（MC3R和MC4R），是主要在大脑中表达的G蛋白偶联受体，它们调节能量稳态的不同方面。MCRs的独特之处在于具有内源性拮抗剂，即刺鼠色蛋白和刺鼠色蛋白相关蛋白（AgRP）。这些拮抗剂后来被证明是反向激动剂。MC3R几乎没有或没有组成性活性，而MC4R具有显著的组成性活性，很容易被检测到。我们在此描述检测这些受体组成性活性的方法以及作为反向激动剂的小分子配体。AgRP是MC3R和MC4R的反向激动剂。我们还提供了组成性激活的MC4R突变体的模型。
