CHARACTERISTICS OF BOVINE PARATHYROID-HORMONE EXTRACTION BY DOG LIVER INVIVO

CHARACTERISTICS OF BOVINE PARATHYROID-HORMONE EXTRACTION BY DOG LIVER INVIVO
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DOI:
10.1152/ajpendo.1981.241.3.e208
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发表时间:
1981-01-01
影响因子:
--
通讯作者:
ROSENBLATT, M
ROSENBLATT, M
中科院分区:
其他
文献类型:
--
作者:
DAMOUR, P;HUET, PM;ROSENBLATT, M

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本文研究了不同~(125)I标记的牛甲状旁腺激素(BPTH)制剂在麻醉犬肝脏单次通过过程中的代谢去向。每个125I-BPTH制剂门静脉注射131I-白蛋白和99mTc-红细胞,2个参比指示物。通过计算肝静脉采集的试管中存在的放射性,得到每个指示剂的稀释曲线。根据这些曲线计算肝血流量(HBF)和肝取出量分数(FHE)。通过比较注射的125I和回收的125I的凝胶色谱图谱,进一步验证了提取结果。注射~(125)I-BPTH-(1-84)后~(125)I的FHE为32.75±-。9.39%(平均+-SD;n=23),平均HbF为48.18±-。11.83毫升.cntdot。Kg-1/min-1。FHE与激素剂量无关,与HbF呈负相关(r=-0.6768,P<0.001)。注射125I-bpth-(1-34)(8)或125I-bpth-(34/43-84)(n=5)后未提取~(125)I。注射~(125)I-bpth-(28-48),18.7±-。~(125)I的萃取率为5.5%(n=8),HbF为47.3±-。17.0毫升.cntdot。Kg-1/min-1。对凝胶图谱的分析进一步揭示了7.6.+-。注射的125I-bpth-(1-84)中4.2%转化为羧基末端片段;13.1+-。125I-bpth-(28-48)和20.9.+-的2.6%。注射的125I-BPTH-(1-34)中有4.9%也被切割成较小的MW产物。序列28-48的完整性对于125I-bpth-(1-84)的FHE是重要的。尽管这个过程不饱和,但它与HBF成反比。完整的甲状旁腺激素或其片段的肝脏失活也通过快速裂解成较小的MW产物进行。
The metabolic fate of various 125I-labeled preparations of bovine parathyroid hormone (bPTH) during a single passage through the liver was studied in anesthetized dogs. Each 125I-bPTH preparation was injected in the portal vein with 131I-albumin and 99mTc-erythrocytes, 2 reference indicators. A dilution curve was obtained for each indicator by counting the radioactivity present in tubes collected by hepatic vein sampling. Hepatic blood flow (HBF) and fractional hepatic extraction (FHE) were calculated from these curves. Extraction results were further validated by comparing the gel chromotography profile of the 125I injected and of the 125I recovered. The FHE of 125I after an injection of 125I-bPTH-(1-84) was 32.75 .+-. 9.39% (mean .+-. SD; n = 23) for a mean HBF of 48.18 .+-. 11.83 ml .cntdot. kg-1 per min-1. The FHE was independent of the dose of hormone injected (0.34-812 ng) but was inversely related to the HBF (r = -0.6768, P < 0.001). 125I was not extracted after an injection of 125I-bPTH-(1-34) (8) or of 125I-bPTH-(34/43-84) (n = 5). After an injection of 125I-bPTH-(28-48), 18.7 .+-. 5.5% (n = 8) of the 125I was extracted for an HBF of 47.3 .+-. 17.0 ml .cntdot. kg-1 per min-1. Analysis of the gel chromotography profiles further disclosed that 7.6 .+-. 4.2% of the 125I-bPTH-(1-84) injected was transformed into carboxyl terminal fragments; 13.1 .+-. 2.6% of the 125I-bPTH-(28-48) and 20.9 .+-. 4.9% of the 125I-bPTH-(1-34) injected were also cleaved into smaller MW products. The integrity of the sequence 28-48 is important for the FHE of 125I-bPTH-(1-84). Although nonsaturable, this process is inversely related to the HBF. Liver inactivation of intact PTH or of its fragments also proceeds through rapid cleavage into smaller MW products.