Physiology and Pharmacology of BRS-3 (Bombesin Receptor Subtype-3)

BRS-3（铃蟾肽受体亚型 3）的生理学和药理学

• 批准号: 8553647
• 负责人: MARC L REITMAN
• 金额: $ 69.66万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8553647
• 关键词: Ablation; Affinity; Agonist; Area; Automobile Driving; Beta Cell; Blood Pressure; Body Temperature; Body Weight; Bombesin; Bombesin Receptor; Brain; Brain Stem; Brown Fat; Cannabinoids; Cardiovascular Diseases; Cell Line; Cell Nucleus; Cells; Cholelithiasis; Comorbidity; Data; Degenerative polyarthritis; Drug Kinetics; Dyslipidemias; Eating; Effectiveness; Fasting; Future; G-Protein-Coupled Receptors; Genetic; Glucose; Goals; Health; Homeostasis; Hypertension; Hypothalamic structure; Investments; Islets of Langerhans; Knock-out; Knockout Mice; Laboratory Research; Leptin; Life Expectancy; Ligands; Malignant Neoplasms; Metabolic; Midbrain structure; Mus; Names; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pharmacology; Physiology; Publications; Regulation; Reproductive Behavior; Research; Rewards; Risk; Rodent; Role; Signal Pathway; Site; Tissues; Transgenic Mice; Work; attenuation; bombesin receptor subtype 3; complement pathway; improved; insulin secretion; interest; member; neuropeptide Y; obesity treatment; recombinase; tool

As part of our studies to elucidate the mechanism of action of BRS-3 agonists, we have preliminary data that BRS-3 agonists increase metabolic rate via stimulating brown adipose tissue. These studies are being confirmed and expanded upon. In order to study the specific cells, sites, tissues, and transmitters by which BRS-3 acts, we are generating the following tools: 1) a conditional knockout floxed Brs3 mouse, 2) a knockin mouse with Cre recombinase driven by Brs3, and 3) a BAC transgenic mouse with Brs3 driving GFP expression. The long-term investment required to generate and validate these tools is expected to yield great rewards in future years. We are collaborating with Merck, using selective BRS-3 compounds (particularly the agonists MK-5046 and MK-7255). Additionally, work on BRS-3 that I was involved with at Merck Research Laboratories prior to my arrival at NIDDK continues to be guided through to publication.

作为我们阐明 BRS-3 激动剂作用机制的研究的一部分，我们有初步数据表明 BRS-3 激动剂通过刺激棕色脂肪组织来提高代谢率。 这些研究正在得到证实和扩展。 为了研究 BRS-3 发挥作用的特定细胞、位点、组织和递质，我们正在开发以下工具：1) 条件性敲除 floxed Brs3 小鼠，2) 具有由 Brs3 驱动的 Cre 重组酶的敲入小鼠，以及3) 具有驱动 GFP 表达的 Brs3 的 BAC 转基因小鼠。 生成和验证这些工具所需的长期投资预计将在未来几年产生巨大的回报。 我们正在与默克公司合作，使用选择性 BRS-3 化合物（特别是激动剂 MK-5046 和 MK-7255）。 此外，我在到达 NIDDK 之前在默克研究实验室参与的 BRS-3 工作将继续得到指导直至发表。