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: 6629686
• 负责人: ABBA J KASTIN
• 金额: $ 18.9万
• 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/6629686
• 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.

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