Korchazhkina O, Wright G, Exley C
Birchall Centre for Inorganic Chemistry and Materials Science, Department of Chemistry, Keele University, Staffordshire, UK.
J Inorg Biochem. 1998 Feb 15;69(3):153-8. doi: 10.1016/s0162-0134(97)10012-5.
ATP is an important extracellular messenger in the coronary vasculature of the heart. To be effective its extracellular concentration must be tightly controlled and this is achieved via ectonucleotidases located in the luminal surface of the coronary endothelium. Al-ATP is a potent inhibitor of the hydrolysis of ATP and we speculated that Al-ATP released by cells into the blood would disrupt the signalling function of extracellular ATP. We tested this hypothesis by perfusing isolated working Wistar rat hearts with buffers containing either ATP or Al-ATP. The functional parameters measured were, coronary flow, heart rate and pulsatile power. A number of control perfusions including adenosine, ATP-gamma-S and Al were used to identify those effects which might be specific to ATP and Al-ATP. Al-ATP did not appear to inhibit the function of the endothelial ectonucleotidases. Both ATP and Al-ATP produced a significant increase in coronary flow and this could be attributed to a coronary vasodilation. Interestingly, whilst the effect of ATP was reversible that of Al-ATP was not. ATP caused a reduction in heart rate which was potentiated by aluminium. The negatively chronotropic effect of Al-ATP was mediated via a mechanism which was either distinct from or in addition to the similar response known to be caused by adenosine. We have demonstrated for the first time an influence of Al-ATP on heart function. Perhaps more pertinently we present the first evidence that Al-ATP may influence the function of ATP-specific receptors.
ATP是心脏冠状动脉血管系统中一种重要的细胞外信使。为了发挥作用，其细胞外浓度必须受到严格控制，这是通过位于冠状动脉内皮腔表面的外核苷酸酶来实现的。Al-ATP是ATP水解的有效抑制剂，我们推测细胞释放到血液中的Al-ATP会破坏细胞外ATP的信号传导功能。我们通过用含有ATP或Al-ATP的缓冲液灌注离体工作的Wistar大鼠心脏来验证这一假设。所测量的功能参数包括冠状动脉血流量、心率和搏动功率。使用了包括腺苷、ATP-γ-S和Al在内的多种对照灌注来确定那些可能是ATP和Al-ATP特有的效应。Al-ATP似乎并未抑制内皮外核苷酸酶的功能。ATP和Al-ATP均使冠状动脉血流量显著增加，这可归因于冠状动脉血管舒张。有趣的是，虽然ATP的作用是可逆的，但Al-ATP的作用却不可逆。ATP导致心率降低，铝可增强这种作用。Al-ATP的负性变时作用是通过一种与已知由腺苷引起的类似反应不同或除此之外的机制介导的。我们首次证明了Al-ATP对心脏功能的影响。或许更相关的是，我们首次提供证据表明Al-ATP可能影响ATP特异性受体的功能。
