Angiotensin II type 1 (AT1) receptor-mediated accumulation of angiotensin II in tissues and its intracellular half-life in vivo.

Angiotensin II type 1 (AT1) receptor-mediated accumulation of angiotensin II in tissues and its intracellular half-life in vivo.
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血管紧张素 II 1 型 (AT1) 受体介导的血管紧张素 II 在组织中的积累及其体内细胞内半衰期。

DOI:
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发表时间:
1997
期刊:
影响因子:
8.3
通讯作者:
M. Schalekamp
M. Schalekamp
中科院分区:
医学1区
文献类型:
--
作者:
J. P. Kats;L. M. Lannoy;A. Danser;J. R. Meegen;P. Verdouw;M. Schalekamp

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血管紧张素II (Ang II)通过受体介导的内吞作用被多种细胞内化。我们对整个动物体内这一过程的动力学以及完整的II型磷酸酶内化后的半衰期知之甚少。我们测量了在猪左心室输注这些肽时,在各种组织和血浆中达到的125I-Ang II和125I-Ang I的水平。骨骼肌、心脏、肾脏和肾上腺中125I-Ang II的稳态浓度分别为动脉血浆中125I-Ang II浓度的8% ~ 41%、64% ~ 150%、340% ~ 550%和680% ~ 2100%(6个实验范围)。125i - angi的组织浓度小于动脉血浆浓度的5%。125I-Ang II在心脏、肾脏和肾上腺的积累几乎完全被一种特异性的1型Ang II (AT1)受体拮抗剂阻断。在30至60分钟内,125I-Ang II在组织中达到稳态浓度,在5分钟内在血浆中达到稳态浓度。完整的125I-Ang II在心脏、肾脏和肾上腺中的体内半衰期约为15分钟,而在循环中的半衰期为0.5分钟。因此,来自循环的Ang II,而不是Ang I,被一些组织积累,这是由AT1受体介导的。这个过程的时间过程和积累的Ang II的长半衰期支持这样的观点,即Ang II在与AT1受体结合后被内化,从而保护它免受内皮肽酶的快速降解。本研究的结果与越来越多的证据一致,即内化Ang II具有重要的生理作用。
Angiotensin II (Ang II) is internalized by various cell types via receptor-mediated endocytosis. Little is known about the kinetics of this process in the whole animal and about the half-life of intact Ang II after its internalization. We measured the levels of 125I-Ang II and 125I-Ang I that were reached in various tissues and blood plasma during infusions of these peptides into the left cardiac ventricle of pigs. Steady-state concentrations of 125I-Ang II in skeletal muscle, heart, kidney, and adrenal were 8% to 41%, 64% to 150%, 340% to 550%, and 680% to 2100%, respectively, of the 125I-Ang II concentration in arterial blood plasma (ranges of six experiments). The tissue concentrations of 125I-Ang I were less than 5% of the arterial plasma concentrations. 125I-Ang II accumulation seen in heart, kidney, and adrenal was almost completely blocked by a specific Ang II type 1 (AT1) receptor antagonist. Steady-state concentrations of 125I-Ang II were reached within 30 to 60 minutes in the tissues and within 5 minutes in blood plasma. The in vivo half-life of intact 125I-Ang II in heart, kidney, and adrenal was approximately 15 minutes, compared with 0.5 minute in the circulation. Thus, Ang II, but not Ang I, from the circulation is accumulated by some tissues, and this is mediated by AT1 receptors. The time course of this process and the long half-life of the accumulated Ang II support the contention that this Ang II has been internalized after its binding to the AT1 receptor, so that it is protected from rapid degradation by endothelial peptidases. The results of this study are in agreement with growing evidence of an important physiological role for internalized Ang II.
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DOI: --
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