Hydroxyurea stimulates the release of ATP from rabbit erythrocytes through an increase in calcium and nitric oxide production.
Hydroxyurea stimulates the release of ATP from rabbit erythrocytes through an increase in calcium and nitric oxide production.
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DOI：
10.1016/j.ejphar.2010.07.012
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发表时间：
2010-10-25
影响因子：
5
通讯作者：
Spence DM
中科院分区：
文献类型：
--
作者：
Raththagala M;Karunarathne W;Kryziniak M;McCracken J;Spence DM
羟基脲是镰状细胞病的一种已证实的治疗方法，已知可改善血流量并减少血管闭塞危象，尽管其确切的作用机制尚不清楚。本研究的目的是确定羟基脲是否通过药物刺激红细胞（RBC）中一氧化氮（NO）产生的能力而导致ATP释放增加。一个系统使红细胞通过微孔管的流动被用来研究ATP从红细胞释放。兔红细胞（7% hct）与50 μM羟基脲孵育后，这些细胞中ATP的释放显著增加。在没有血流的情况下，没有检测到这种水平的ATP释放。研究还表明，羟脲和一氧化氮（来自精子enonoate）的增加导致ATP释放最初增加，随后在更高浓度的羟脲和一氧化氮供体中释放减少。用L-NAME孵育消除了羟基脲的作用，表明红细胞参与了NO的产生。事实上，在50 μM羟基脲的存在下，在7%的红细胞溶液中测量到的总Ca2+量（通过原子吸收光谱）从363±47 ng/ml增加到530±52 ng/ml。最后，EPR研究表明，RBC中亚硝基化Hb的增加仅在涉及羟基脲和含Ca2+缓冲液的研究中测量。
Hydroxyurea, a proven therapy for sickle cell disease, is known to improve blood flow and reduce vaso-occlusive crises, although its exact mechanism of action is not clear. The objective of this study was to determine if hydroxyurea results in an increase of ATP release from the red blood cell (RBC) via the drug's ability to stimulate nitric oxide (NO) production in these cells. A system enabling the flow of RBCs through microbore tubing was used to investigate ATP release from the RBC. Incubation of rabbit RBCs (7% hct) with 50 μM hydroxyurea resulted in a significant increase in the release of ATP from these cells. This level of ATP release was not detected in the absence of flow. Studies also showed that increments in hydroxyurea and NO (from spermineNONOate) resulted in an initial increase in ATP release, followed by a decrease in this release at higher concentrations of hydroxyurea and the NO donor. Incubation with L-NAME abolished the effect of the hydroxyurea, suggesting that NO production by the RBC was involved. Indeed, in the presence of 50 μM hydroxyurea, the amount of total Ca2+ measured (by atomic absorption spectroscopy) in a 7% solution of RBCs increased from 363 ± 47 ng/ml and 530 ± 52 ng/ml. Finally, EPR studies suggest that an increase in nitrosylated Hb in the RBC is only measured for those studies involving hydroxyurea and a Ca2+-containing buffer.
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DOI：
10.1016/j.biocel.2006.01.010
发表时间：
2006-01-01
影响因子：
4
作者：
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通讯作者：
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影响因子：
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DOI：
10.1152/ajpheart.01233.2008
发表时间：
2009-10-01
影响因子：
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作者：
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