PEPTIDES AND ALCOHOL INTERACT AT THE BLOOD-BRAIN BARRIER

描述： 血脑屏障 (BBB) 不再被视为静态墙 限制大脑循环肽。许多肽已被证明 穿透血脑屏障，有些通过扩散，有些通过选择性转运 机制。 BBB 上的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位点。它是 提出酒精会增加血管紧张素 II (AT) 的进入， 胆囊收缩素-8 (CCK)、瘦素和肿瘤坏死因子-α (TNF) 大脑中的血液循环，从而抑制酒精的摄入。的影响 酒精摄入对进入酒精的速率和饱和度（自我抑制）的影响 将 AT、CCK、瘦素和 TNF 外周注射到小鼠大脑中 通过多次回归分析和无血灌注确定。 HPLC 将确定静脉注射物质完好无损地到达大脑， 毛细管耗尽与冲洗将表明它不与 毛细血管内皮或与血管成分松散相关，以及 测量大脑流出量将排除可能的混杂影响 涌入。同时注射白蛋白可控制血液渗漏 和非特定条目。交叉抑制，特别是 TNF 对瘦素的交叉抑制 运输，将确定 TNF 是否影响 BBB 处的瘦素，就像它在 脂肪细胞。酒精诱导这四种物质进入大脑 可能至少部分是由与其不同的转运蛋白介导的 受体。在分离和鉴定这些转运蛋白后， 乙醇对其在大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。这些敏感程序将表明 BBB 是酒精和肽相互作用的动态位点。

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.