ALPHA ADRENERGIC REGULATION OF BROWN ADIPOSE TISSUE

棕色脂肪组织的 ALPHA 肾上腺素调节

• 批准号: 3234427
• 负责人: RICHARD J SCHIMMEL
• 金额: $ 10.92万
• 依托单位: UNIV OF MED/DENT NJ-SCH OSTEOPATHIC MED
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3234427
• 关键词: adenosine; adenylate cyclase; adrenergic agents; alpha adrenergic receptor; arachidonate; autoradiography; bioenergetics; brown fat; catecholamines; cellular respiration; diacylglycerols; fluorescent dye /probe; guanosine triphosphate; hamsters; heat; inositol phosphates; lipid metabolism; lipolysis; membrane activity; mitochondria; oxygen consumption; phenylephrine; phosphatidate; phosphatidylinositols; phospholipase C; phospholipids; radiotracer; thin layer chromatography

The research proposed herein will investigate the cellular mechanisms which underlie the regulation of thermogenesis in hamster brown adipocytes. Thermogenesis in brown fat cells is subject to bimodal regulation: stimulation by catecholamines acting via both beta and alpha-1 adrenergic receptors and inhibition by adenosine, acting via A1 type receptors. Adenosine is capable of antagonizing the thermogenic response to both beta or alpha adrenergic receptors. The mechanisms underlying the thermogenic response to alpha adrenergic receptors are enigmatic as are the mechanisms underlying adenosine modulation of this response and the elucidation of both are long term objectives of this research project. The thermogenic response to activation of alpha-1 adrenergic receptors is associated with the activation of both phospholipase C and phospholipase A2 causing the breakdown of phosphoinositides and other membrane phospholipids and the accumulation of inositol phosphates, diacylglcerol and arachidonic acid. The present research seeks a more detailed understanding of alpha adrenergic regulation of phospholipid metabolism in these cells by studying phospholipase C and A2 activities in plasma membranes isolated from brown adipocytes. Subsequent experiments will investigate the mechanisms by which adenosine antagonizes the cellular responses to alpha-1 receptor activation. These experiments will test the hypothesis that adenosine acts by uncoupling alpha-1 receptors from either phospholipase C or phospholipase A2, and acts as an inhibitor of phosphoinositide breakdown and/or production of arachidonic acid in these cells. These studies will provide insight into the biochemical regulation of thermogenesis and will contribute information on the bimodal regulation of phospholipid metabolism in a unique cell type not previously investigated.

本文提出的研究将研究细胞 基于调节热发生的机制 仓鼠棕色脂肪细胞。 棕色脂肪细胞中的热发生是 受双峰调节的约束：儿茶酚胺刺激 通过Beta和Alpha-1肾上腺素能受体以及 腺苷抑制作用，通过A1型受体作用。 腺苷是 能够拮抗对β或 α肾上腺素能受体。 依据的机制 对α肾上腺素能受体的热反应是神秘的 以及对此的腺苷调制的基础机制也是 响应和阐明都是长期目标的 这个研究项目。 对激活的热反应 α-1肾上腺素能受体与激活有关 磷脂酶C和磷脂酶A2引起分解 磷酸肌醇和其他膜磷脂以及 肌醇磷酸盐，二酰基甘油和蛛网膜含量的积累 酸。 本研究寻求更详细的理解 这些磷脂代谢的α肾上腺素能调节 通过研究血浆中的磷脂酶C和A2活性 从棕色脂肪细胞中分离出来的膜。 随后的 实验将研究腺苷的机制 拮抗对α-1受体激活的细胞反应。 这些实验将检验以下假设：腺苷通过 从磷脂酶C或 磷脂酶A2，充当磷酸肌醇的抑制剂 在这些细胞中分解和/或产生花生四烯酸。 这些研究将提供对生化调节的见解 热生成，并将为双峰贡献信息 调节独特细胞类型中磷脂代谢的调节 先前已调查。