Molecular pharmacology of beta adrenoreceptors in multiple disease states

多种疾病状态下β肾上腺素受体的分子药理学

• 批准号: nhmrc : 124407
• 负责人: Prof Roger Summers
• 金额: $ 38.6万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/molecular-pharmacology-beta-disease-states/101053
• 关键词: Molecular; pharmacology; beta; adrenoreceptors; multiple

Obesity is a major and increasing health concern for almost half the adult population, and is associated with serious medical conditions including diabetes and heart disease. Changes in behaviour such as increasing physical activity and eating less high-calorie food help many people reduce their body weight, however many others have a genetic predisposition to become overweight and behavioural measures are ineffective. Although anti-obesity drugs should be a valuable adjunct to lifestyle changes, the currently available appetite suppressants are not ideal. Our work involves studying particular cell-surface proteins (receptors) which normally respond to hormones such as adrenaline. The beta(3)-adrenergic receptor is known to mediate the breakdown of fats and increased heat production in adipose tissue and possibly muscle. Administration of beta(3)-selective drugs to obese mice promotes weight loss and a reduction of diabetic symptoms, and a number of drugs targetting the human beta(3)-adrenergic receptor are being developed by pharmaceutical companies. We are trying to understand more about the properties of this receptor, as this information will assist in designing drugs which are more selective and more potent. Sometimes drugs act at more than one receptor, and there is evidence that this may be the case for two drugs called CGP 12177 and BRL 37344 which stimulate the beta(3)-adrenergic receptor. The second major aim of our project is to find out whether these drugs act at a novel receptor which is related to the beta(3)-adrenergic receptor and also mediates energy expenditure and heat production in adipose tissue and skeletal muscle. The discovery of a new receptor would provide additional scope for the development of effective anti-obesity treatments.

肥胖是近一半成年人口的主要和日益严重的健康问题，并与包括糖尿病和心脏病在内的严重医疗状况有关。行为的改变，如增加体育活动和少吃高热量食物，有助于许多人减轻体重，但许多其他人有超重的遗传倾向，行为措施无效。尽管抗肥胖药物应该是改变生活方式的有价值的辅助手段，但目前可用的食欲抑制剂并不理想。我们的工作包括研究特定的细胞表面蛋白质（受体），这些蛋白质通常会对肾上腺素等激素产生反应。已知β（3）-肾上腺素能受体介导脂肪分解并增加脂肪组织和可能肌肉中的产热。向肥胖小鼠施用β（3）选择性药物可促进体重减轻和糖尿病症状减轻，制药公司正在开发多种针对人类β（3）肾上腺素能受体的药物。我们正试图更多地了解这种受体的特性，因为这些信息将有助于设计更具选择性和更有效的药物。有时，药物会作用于多个受体，有证据表明，两种名为CGP 12177和BRL 37344的药物可能属于这种情况，它们会刺激β（3）-肾上腺素能受体。我们项目的第二个主要目的是发现这些药物是否作用于与β（3）-肾上腺素能受体相关的新受体，并介导脂肪组织和骨骼肌中的能量消耗和产热。新受体的发现将为开发有效的抗肥胖治疗提供额外的空间。