Ohki-Hamazaki H, Watase K, Yamamoto K, Ogura H, Yamano M, Yamada K, Maeno H, Imaki J, Kikuyama S, Wada E, Wada K
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Nature. 1997 Nov 13;390(6656):165-9. doi: 10.1038/36568.
Mammalian bombesin-like peptides are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism and behaviour. They bind to G-protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors cloned so far include, gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). However, despite the molecular characterization of BRS-3, determination of its function has been difficult as a result of its low affinity for bombesin and its lack of an identified natural ligand. We have generated BRS-3-deficient mice in an attempt to determine the in vivo function of the receptor. Mice lacking functional BRS-3 developed a mild obesity, associated with hypertension and impairment of glucose metabolism. They also exhibited reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia. Our data suggest that BRS-3 is required for the regulation of endocrine processes and metabolism responsible for energy balance and adiposity. BRS-3-deficient mice provide a useful new model for the investigation of human obesity and associated diseases.
哺乳动物的蛙皮素样肽广泛分布于中枢神经系统以及胃肠道，在这些部位它们调节平滑肌收缩、外分泌和内分泌过程、新陈代谢及行为。它们与细胞表面的G蛋白偶联受体结合以发挥作用。迄今克隆出的蛙皮素样肽受体包括胃泌素释放肽受体（GRP-R）、神经介素B受体（NMB-R）和蛙皮素受体亚型3（BRS-3）。然而，尽管对BRS-3进行了分子特征鉴定，但由于它对蛙皮素的亲和力低且缺乏已确定的天然配体，其功能的确定一直很困难。我们培育出了BRS-3基因缺失的小鼠，试图确定该受体在体内的功能。缺乏功能性BRS-3的小鼠出现了轻度肥胖，伴有高血压和葡萄糖代谢受损。它们还表现出代谢率降低、进食效率提高以及随后的食欲亢进。我们的数据表明，BRS-3对于调节负责能量平衡和肥胖的内分泌过程及新陈代谢是必需的。BRS-3基因缺失的小鼠为研究人类肥胖及相关疾病提供了一个有用的新模型。
