Nishiyama A, Kimura S, He H, Miura K, Rahman M, Fujisawa Y, Fukui T, Abe Y
Department of Pharmacology, Kagawa Medical University, Kagawa 761-0793, Japan.
Am J Physiol Renal Physiol. 2001 Feb;280(2):F231-8. doi: 10.1152/ajprenal.2001.280.2.F231.
The present study was conducted to determine the metabolism of renal interstitial adenosine under resting conditions and during ischemia. By using a microdialysis method with HPLC-fluorometric analysis, renal interstitial concentrations of adenosine, inosine, and hypoxanthine were assessed in pentobarbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 +/- 0.04, 0.31 +/- 0.05, and 0.35 +/- 0.05 micromol/l, respectively. Local inhibition of adenosine kinase with iodotubercidin (10 micromol/l in perfusate) or inhibition of adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 100 micromol/l in perfusate) did not change adenosine concentrations in the nonischemic kidneys (0.18 +/- 0.04 and 0.24 +/- 0.05 micromol/l, respectively). On the other hand, treatment with iodotubercidin+EHNA significantly increased adenosine concentration (0.52 +/- 0.07 micromol/l) with significant decreases in inosine and hypoxanthine levels (0.13 +/- 0.03 and 0.19 +/- 0.04 micromol/l, respectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 +/- 0.29, 2.14 +/- 0.45, and 21.8 +/- 4.7 micromol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 +/- 0.18 micromol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 +/- 2.16 micromol/l), the value of which was not augmented by an addition of iodotubercidin (15.80 +/- 1.24 micromol/l). In contrast, ischemia-induced increases in inosine and hypoxanthine were inversely diminished by the treatment with iodotubercidin+EHNA (0.90 +/- 0.20 and 9.86 +/- 1.96 micromol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contribute to the metabolism of renal interstitial adenosine under resting conditions, whereas adenosine produced during ischemia is mainly metabolized by adenosine deaminase and the rephosphorylation of adenosine by adenosine kinase is small.sent
本研究旨在确定静息状态下及缺血期间肾间质腺苷的代谢情况。通过使用微透析法结合高效液相色谱 - 荧光分析，在戊巴比妥麻醉的犬中评估肾间质中腺苷、肌苷和次黄嘌呤的浓度。腺苷、肌苷和次黄嘌呤的平均基础肾间质浓度分别为0.18±0.04、0.31±0.05和0.35±0.05微摩尔/升。用碘结核菌素（灌注液中10微摩尔/升）局部抑制腺苷激酶或用erythro - 9 -（2 - 羟基 - 3 - 壬基）腺嘌呤（EHNA；灌注液中100微摩尔/升）抑制腺苷脱氨酶，并未改变非缺血肾脏中的腺苷浓度（分别为0.18±0.04和0.24±0.05微摩尔/升）。另一方面，用碘结核菌素+EHNA处理显著增加了腺苷浓度（0.52±0.07微摩尔/升），同时肌苷和次黄嘌呤水平显著降低（分别为0.13±0.03和0.19±0.04微摩尔/升）。在缺血30分钟期间，腺苷、肌苷和次黄嘌呤分别显著增加至0.76±0.29、2.14±0.45和21.8±4.7微摩尔/升。用碘结核菌素处理未改变缺血诱导的腺苷增加（0.84±0.18微摩尔/升）；然而，单独使用EHNA显著增强了腺苷积累（13.54±2.16微摩尔/升），添加碘结核菌素后该值并未增加（15.80±1.24微摩尔/升）。相反，碘结核菌素+EHNA处理使缺血诱导的肌苷和次黄嘌呤增加呈反向减少（分别为0.90±0.20和9.86±1.96微摩尔/升）。这些结果表明，在静息状态下，腺苷激酶和腺苷脱氨酶均参与肾间质腺苷的代谢，而缺血期间产生的腺苷主要由腺苷脱氨酶代谢，腺苷激酶对腺苷的再磷酸化作用较小。
