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: 6881278
• 负责人: ABBA J KASTIN
• 金额: $ 22.05万
• 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/6881278
• 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.

描述： 血脑屏障（BBB）不再被视为静态墙 限制大脑循环肽。已经显示了许多肽 要穿透BBB，有些通过扩散，有些是通过选择性传输的 机制。 BBB酒精与某些肽的相互作用 可以影响酒精摄入将提供一个新的调节部位。这是 提出酒精会增加血管紧张素II（AT）的进入 胆囊基蛋白8（CCK），瘦素和肿瘤坏死因子-Alpha（TNF）进入 循环中的大脑，从而抑制酒精摄入。效果 酒精摄入的速度和饱和度（自抑制） 在CCK，瘦素和TNF的外围注射到小鼠的大脑中 通过多次回归分析和无血液灌注确定。 HPLC将确定静脉注射的物质完整到达大脑， 毛细管耗尽的用水将表明它不绑定到 毛细血管内皮或与血管元素松散相关，并且 从大脑中的流出测量将排除对可能的混杂影响 涌入。同时注射白蛋白将控制血液泄漏 和非特异性进入。交叉抑制，特别是TNF在瘦素上 运输，将确定TNF是否像在BBB处影响瘦素 脂肪细胞。酒精引起的这四种物质进入大脑 可能至少是由转运蛋白部分介导的 受体。在分离和鉴定这些转运蛋白之后， 乙醇对大脑分布的影响将通过 放射自显影图像分析。这些敏感的程序将表明 BBB是酒精和肽相互作用的动态部位。