PEPTIDES AND ALCOHOL INTERACT AT THE BLOOD-BRAIN BARRIER

肽和酒精在血脑屏障处相互作用

• 批准号: 6967737
• 负责人: ABBA J KASTIN
• 金额: $ 13.04万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967737
• 关键词: active transport; albumins; alcoholic beverage consumption; alcohols; angiotensin II; blood brain barrier; cholecystokinin; high performance liquid chromatography; intermolecular interaction; laboratory mouse; leptin; membrane permeability; protein transport; tumor necrosis factor alpha

DESCRIPTION: The blood-brain barrier (BBB) is no longer considered a static wall restricting circulating peptides from the brain. Many peptides have been shown to penetrate the BBB, some by diffusion and some by selective transport mechanisms. The interaction of alcohol at the BBB with certain peptides that can affect alcohol ingestion would provide a novel site of regulation. It is proposed that alcohol increases the entry of angiotensin II (AT), cholecystokinin-8 (CCK), leptin, and tumor necrosis factor-alpha (TNF) into brain from the circulation, thus inhibiting alcohol ingestion. The effects of alcohol ingestion on the rate and saturation (self-inhibition) of entry of peripherally injected AT, CCK, leptin, and TNF into the brains of mice will be determined by multiple-time regression analysis and also blood-free perfusion. HPLC will determine that the iv injected substance reaches the brain intact, capillary depletion with washout will show that it is not bound to the capillary endothelium or loosely associated with vascular elements, and measurement of efflux from brain will rule out possible confounding effects on influx. Simultaneous injection of albumin will control for leakage of blood and non-specific entry. Cross-inhibition, particularly of TNF on leptin transport, will determine whether TNF affects leptin at the BBB as it does at the adipocyte. Alcohol-induced transport of these four substances into brain is probably at least partially mediated by transporters different from their receptors. After the isolation and identification of these transport proteins, the effects of ethanol on their distribution in brain will be quantified by autoradiographic image analysis. These sensitive procedures will show that the BBB serves as a dynamic site for the interaction of alcohol and peptides.

产品说明： 血脑屏障（BBB）不再被认为是一个静态的墙 限制大脑中循环的肽。许多肽已经被证明 穿透血脑屏障，有些通过扩散，有些通过选择性转运 机制等酒精在血脑屏障与某些肽的相互作用， 可以影响酒精摄入，这将提供一个新的调节位点。是 提出酒精增加血管紧张素II（AT）的进入， 胆囊收缩素-8（CCK）、瘦素和肿瘤坏死因子-α（TNF）， 大脑从循环，从而抑制酒精摄入。的影响 酒精摄入对进入的速率和饱和度（自我抑制） 将外周注射AT、CCK、瘦素和TNF到小鼠脑中， 通过多次回归分析以及无血灌注确定。 HPLC将确定静脉注射的物质完整地到达大脑， 毛细血管消耗与冲洗将表明它不结合到 毛细血管内皮或与血管成分松散相关，以及 测量脑外排将排除可能的混杂效应， 流入。同时注射白蛋白将控制血液渗漏 非特定条目。交叉抑制，特别是TNF对瘦素的交叉抑制 运输，将决定是否TNF影响瘦素在血脑屏障，因为它在 脂肪细胞酒精诱导这四种物质进入大脑 可能至少部分是由转运蛋白介导的， 受体。在分离和鉴定了这些转运蛋白后， 乙醇对它们在脑中分布的影响将通过以下方式量化： 放射自显影图像分析。这些敏感的程序将表明， 血脑屏障是醇与肽相互作用的动力学位点。