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双嘧达莫是如何提高细胞外腺苷浓度的?腺苷生成与失活三室模型的预测。

How does dipyridamole elevate extracellular adenosine concentration? Predictions from a three-compartment model of adenosine formation and inactivation.

作者信息

Newby A C

出版信息

Biochem J. 1986 Aug 1;237(3):845-51. doi: 10.1042/bj2370845.

DOI:10.1042/bj2370845
PMID:3800923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1147065/
Abstract

Steady-state mathematical models are developed according to which adenosine is formed in the cytoplasm of a group of cells, arises in the extracellular space via the symmetric nucleoside transporter and is inactivated in the adenosine forming cells and after rate-limiting transport into other cell-types. Dipyridamole increases the Km and Vmax. of the transporter symmetrically with respect to influx and efflux. Models incorporating differing degrees of compartmentation are used to predict intracellular and extracellular adenosine concentration as a function of dipyridamole concentration and adenosine formation rate. The vasodilator action of dipyridamole is explained since it is predicted to elevate interstitial fluid adenosine concentrations at all rates of adenosine formation provided that washout of the interstitial compartment is restricted.

摘要

稳态数学模型的建立基于这样的假设

腺苷在一组细胞的细胞质中形成,通过对称核苷转运体出现在细胞外空间,并在形成腺苷的细胞中以及在限速转运到其他细胞类型后失活。双嘧达莫对称地增加了转运体的Km和Vmax,其流入和流出的情况相同。采用包含不同程度分隔的模型来预测细胞内和细胞外腺苷浓度与双嘧达莫浓度及腺苷形成速率的函数关系。双嘧达莫的血管舒张作用得到了解释,因为据预测,只要间质隔室的清除受到限制,在所有腺苷形成速率下,它都会提高间质液中腺苷的浓度。

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How does dipyridamole elevate extracellular adenosine concentration? Predictions from a three-compartment model of adenosine formation and inactivation.双嘧达莫是如何提高细胞外腺苷浓度的?腺苷生成与失活三室模型的预测。
Biochem J. 1986 Aug 1;237(3):845-51. doi: 10.1042/bj2370845.
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本文引用的文献

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A common basis for inhibition of nucleoside transport by dipyridamole and nitrobenzylthioinosine?双嘧达莫和硝基苄硫基肌苷抑制核苷转运的共同基础?
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Role of S-adenosylhomocysteine hydrolase in adenosine metabolism in mammalian heart.S-腺苷同型半胱氨酸水解酶在哺乳动物心脏腺苷代谢中的作用。
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The control of adenosine concentration in polymorphonuclear leucocytes, cultured heart cells and isolated perfused heart from the rat.大鼠多形核白细胞、培养的心脏细胞和离体灌注心脏中腺苷浓度的控制。
Biochem J. 1983 Aug 15;214(2):317-23. doi: 10.1042/bj2140317.
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Inward fluxes of adenosine in erythrocytes and cultured cells measured by a quenched-flow method.通过猝灭流动法测量红细胞和培养细胞中腺苷的内向通量。
Biochem J. 1984 Dec 15;224(3):1001-8. doi: 10.1042/bj2241001.
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Effects of dipyridamole on myocardial adenosine and active hyperemia.双嘧达莫对心肌腺苷及主动性充血的影响。
Am J Physiol. 1984 Nov;247(5 Pt 2):H804-10. doi: 10.1152/ajpheart.1984.247.5.H804.
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Theophylline antagonizes cardiovascular responses to dipyridamole in man without affecting increases in plasma adenosine.茶碱可拮抗人体对双嘧达莫的心血管反应,而不影响血浆腺苷水平的升高。
Acta Physiol Scand. 1984 Jun;121(2):165-71. doi: 10.1111/j.1748-1716.1984.tb07443.x.
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Release of two vasodilators, adenosine and prostacyclin, from isolated rabbit hearts during controlled hypoxia.在控制性低氧期间,从离体兔心脏释放两种血管舒张剂,即腺苷和前列环素。
J Physiol. 1983 Jul;340:487-501. doi: 10.1113/jphysiol.1983.sp014775.