Pospísil M, Hofer M, Vacek A, Netíková J, Pipalová I, Viklická S
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno.
Physiol Res. 1993;42(5):333-40.
Recent results of the authors have demonstrated that the elevation of extracellular adenosine induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), a soluble adenosine prodrug, mediates radioprotective effects in mice. Furthermore, it has been shown that this action is induced by at least two mechanisms: (1) protection by hypoxia as a result of the effects of treatment on the cardiovascular system (bradycardia, vasodilation), and (2) an enhanced regeneration of the radiation-perturbed hematopoiesis. Here, it was ascertained that the joint use of an optimal dose of noradrenaline given with dipyridamole and AMP combination eliminates the hypothermic and hypoxic effects of the treatment, but preserves the radioprotective action of dipyridamole and AMP combination in terms of hematopoietic recovery and partially also survival enhancing effects of the drugs in gamma-irradiated mice. These findings might be of importance for attempts to obtain available and tolerable radioprotective pharmacological prescriptions for clinical use.
作者最近的研究结果表明,联合使用双嘧达莫(一种抑制细胞摄取腺苷的药物)和腺苷一磷酸(AMP,一种可溶性腺苷前药)所诱导的细胞外腺苷水平升高,可介导对小鼠的辐射防护作用。此外,研究表明这种作用至少由两种机制诱导:(1)由于治疗对心血管系统的影响(心动过缓、血管舒张)导致缺氧保护,以及(2)辐射干扰的造血功能增强再生。在此,已确定与双嘧达莫和AMP组合一起给予最佳剂量的去甲肾上腺素,可消除治疗的体温过低和缺氧作用,但在造血恢复方面保留了双嘧达莫和AMP组合的辐射防护作用,并且在一定程度上也保留了这些药物对γ射线照射小鼠的存活增强作用。这些发现对于尝试获得可用于临床的有效且可耐受的辐射防护药理学处方可能具有重要意义。