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.
复制标题
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。
作者:
J. P. Kats;L. M. Lannoy;A. Danser;J. R. Meegen;P. Verdouw;M. Schalekamp
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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影响因子:
4.8
作者:
Tang,SS;Rogg,H;Schumacher,R;Dzau,VJ
通讯作者:
Dzau,VJ
DOI:
10.1172/jci116139
发表时间:
1992
期刊:
The Journal of clinical investigation
影响因子:
--
作者:
Schelling,JR;Hanson,AS;Marzec,R;Linas,SL
通讯作者:
Linas,SL
影响因子:
8.3
作者:
L. Zou;J. Imig;A. V. Thun;A. Hymel;H. Ono;L. Navar
通讯作者:
L. Zou;J. Imig;A. V. Thun;A. Hymel;H. Ono;L. Navar
DOI:
--
发表时间:
1989
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
Kiron,MA;Soffer,RL
通讯作者:
Soffer,RL
DOI:
--
发表时间:
1987
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
Griendling,KK;Delafontaine,P;Rittenhouse,SE;GimbroneJr,MA;Alexander,RW
通讯作者:
Alexander,RW