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: 6211433
• 负责人: ABBA J KASTIN
• 金额: $ 21.4万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 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/6211433
• 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.

说明： 血脑屏障(Bbb)不再被认为是一堵静态的墙。 限制大脑中的多肽循环。已经展示了许多多肽 为了穿透BBB，有些是通过扩散，有些是通过选择性传输 机制。酒精在血脑屏障与某些多肽的相互作用 能够影响酒精摄取将提供一个新的调节场所。它是 提出酒精增加血管紧张素II(AT)的进入， CCK、瘦素和肿瘤坏死因子-α 大脑循环，从而抑制酒精摄取。的影响 酒精摄入对大脑皮层进入的速率和饱和度(自我抑制)的影响 将AT、CCK、瘦素和肿瘤坏死因子外周注射到小鼠脑内 经多次回归分析和无血灌流测定。 高效液相色谱法将确定静脉注射的物质完好无损地到达大脑， 毛细管的冲刷耗尽将表明它不与 毛细血管内皮细胞或与血管分子松散结合，以及 测量大脑的外流将排除可能的混杂影响 涌入。同时注射白蛋白将控制血液渗漏 和非特定条目。瘦素的交叉抑制作用，尤其是肿瘤坏死因子 运输，将决定肿瘤坏死因子是否影响血脑屏障中的瘦素 脂肪细胞。酒精诱导的这四种物质的脑内转运 可能至少部分由不同于他们的转运体的转运体介导 感受器。在分离和鉴定这些运输蛋白之后， 乙醇对它们在大脑中分布的影响将通过以下方法来量化 放射自显影图像分析。这些敏感的程序将表明， 血脑屏障是酒精和多肽相互作用的动态场所。