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肝实质细胞中受体介导的胰岛素和催乳素内吞作用的差异动力学及对氯喹的敏感性

Differential kinetics and sensitivity to chloroquine of receptor-mediated insulin and prolactin endocytosis in liver parenchymal cells.

作者信息

Khan M N, Savoie S, Bergeron J J, Posner B I

出版信息

Biochim Biophys Acta. 1986 Aug 29;888(1):100-6. doi: 10.1016/0167-4889(86)90075-3.

DOI:10.1016/0167-4889(86)90075-3
PMID:3017440
Abstract

Systemically injected [125I]prolactin or [125I]insulin was accumulated and cleared from rat liver at different rates. Quantitative subcellular fractionation indicated a predominant accumulation of [125I]insulin in liver microsomes while [125I]prolactin was found in both the light-mitochondrial and microsomal fractions. The acidotropic agent chloroquine diminished the rate and extent of loss of each ligand from liver homogenates. In chloroquine treated rats, radiolabeled insulin accumulated in both the light-mitochondrial and the microsomal fractions. Subfraction of microsomes on discontinuous sucrose gradients revealed "early' endosomes in which ligand uptake was maximal at 2-5 min. In contrast, comparable subfraction of the of light mitochondrial fraction revealed "late' endosomes in which ligand uptake was maximal at 10-20 min. Chloroquine-treated rats showed a more marked enhancement of insulin compared to prolactin uptake in the "early' endosomes. It is suggested that "early' endosomes found in the Golgi-intermediate and -heavy fractions floated from parent microsomes may selectively degrade insulin but not prolactin. This could account for the apparently different kinetics of insulin and prolactin uptake into liver parenchyma.

摘要

经全身注射的[125I]催乳素或[125I]胰岛素以不同速率在大鼠肝脏中蓄积和清除。定量亚细胞分级分离表明,[125I]胰岛素主要蓄积在肝脏微粒体中,而[125I]催乳素则存在于轻线粒体和微粒体组分中。亲酸性药物氯喹降低了每种配体从肝脏匀浆中丢失的速率和程度。在氯喹处理的大鼠中,放射性标记的胰岛素蓄积在轻线粒体和微粒体组分中。在不连续蔗糖梯度上对微粒体进行亚分级分离,发现了“早期”内体,其中配体摄取在2 - 5分钟时达到最大值。相比之下,对轻线粒体组分进行类似的亚分级分离,发现了“晚期”内体,其中配体摄取在10 - 20分钟时达到最大值。氯喹处理的大鼠在“早期”内体中胰岛素摄取比催乳素摄取有更明显的增强。有人提出,在高尔基体中间和重质组分中发现的、从亲本微粒体漂浮而来的“早期”内体可能选择性地降解胰岛素而不是催乳素。这可以解释胰岛素和催乳素摄取到肝实质中明显不同的动力学。

相似文献

1
Differential kinetics and sensitivity to chloroquine of receptor-mediated insulin and prolactin endocytosis in liver parenchymal cells.肝实质细胞中受体介导的胰岛素和催乳素内吞作用的差异动力学及对氯喹的敏感性
Biochim Biophys Acta. 1986 Aug 29;888(1):100-6. doi: 10.1016/0167-4889(86)90075-3.
2
Differential and analytical subfractionation of rat liver components internalizing insulin and prolactin.大鼠肝脏中内化胰岛素和催乳素的成分的差异分离与分析亚分级分离
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Prolactin uptake into liver endocytic components. Reduced sensitivity to chloroquine.
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引用本文的文献

1
Fate of injected glucagon taken up by rat liver in vivo. Degradation of internalized ligand in the endosomal compartment.大鼠肝脏在体内摄取的注射用胰高血糖素的命运。内体区室内内化配体的降解。
Biochem J. 1990 Dec 15;272(3):703-12. doi: 10.1042/bj2720703.