STUDIES OF BLOOD-CEREBROSPINAL FLUID BARRIER TO CORTISOL IN DOG
STUDIES OF BLOOD-CEREBROSPINAL FLUID BARRIER TO CORTISOL IN DOG
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DOI：
10.1172/jci104426
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发表时间：
1961-01-01
影响因子：
15.9
通讯作者：
FISHMAN, RA
中科院分区：
文献类型：
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作者：
CHRISTY, NP;FISHMAN, RA
麻醉犬脑脊液中皮质醇静息浓度低于1 [mu]g/100 ml。静脉注射皮质醇或半乙酰皮质醇-21后，类固醇迅速进入脑脊液，在5-30分钟内出现。在一项单次实验中，延长输注皮质醇-21-半琥珀酸4小时后，脑脊液/血浆的稳定比值达到0.2。这可以解释为反映了80%的皮质醇与血浆蛋白结合。注射皮质醇或皮质醇-21-半琥珀酸后，脑脊液中只出现游离（未结合的）类固醇，而不是皮质醇代谢产物的葡萄糖醛酸盐，尽管在血浆和尿液中发现了一种共轭代谢产物四氢皮质醇葡萄糖醛酸盐的高浓度。这些发现与大多数药物和天然产物的发现一致，即非极性、水不溶性物质比极性、水溶性化合物更容易从血液进入脑脊液。皮质醇的另一种代谢产物，四氢化可的松可以自由进入脑脊液，但四氢化可的松葡萄糖醛酸不能。四氢化可的松比皮质醇进入脑脊液的速度更快，这可能是因为前者与血浆蛋白的结合程度较低。在狗身上，皮质醇只被代谢为四氢皮质醇，而不是像人那样被代谢为四氢皮质醇、四氢皮质醇和四氢可的松。ACTH给药11天没有改变皮质醇进入CSF或血浆给药类固醇的“一半时间”。
The resting concentration of cortisol in cerebrospinal fluid is less than 1 [mu]g/100 ml in the anesthetized dog. After intravenous injection of cortisol or cortisol-21-hemisuccinate, the steroid enters the CSF rapidly, appearing there within 5-30 minutes. In a single experiment prolonged infusion of cortisol-21-hemisuccinate resulted by the 4th hour in the attainment of a steady state ratio, CSF/plasma, of 0.2. This can be interpreted as reflecting an 80% binding of cortisol to plasma protein. After cortisol or cortisol-21-hemisuccinate injection, only free (unconjugated) steroid, not the glucuronides of cortisol metabolites, appears in CSF, although a conjugated metabolic product, tetrahydrocortisol glucuronide is found in high concentration in plasma and urine. These findings are in accord with those concerning most drugs and natural products, i.e., that nonpolar, water-insoluble substances enter CSF from blood more readily than do polar, water-soluble compounds. Another metabolic product of cortisol, tetrahydro-cortisone freely enters the CSF, but tetrahydrocortisone glucuronide does not. The more rapid entry into CSF of tetrahydrocortisone than of cortisol may be explained by the lesser degree of binding to plasma protein of the former steroid. In the dog, cortisol is metabolized to tetrahydrocortisol only, not to tetrahydrocortisol, allo-tetrahydro-cortisol and tetrahydrocortisone, as in man. ACTH administration for 11 days did not alter cortisol entry into CSF or plasma "half-time" of administered steroid.