Achterberg P W, Harmsen E, de Jong J W
Cardiovasc Res. 1985 Oct;19(10):593-8. doi: 10.1093/cvr/19.10.593.
Quantitative determination of myocardial adenosine formation and breakdown is necessary to gain insight into the mechanism and regulation of its physiological actions. Deamination of adenosine was studied in isolated perfused rat hearts by infusion of adenosine (1 to 20 mumol X litre-1). All catabolites in the perfusates (inosine, hypoxanthine, xanthine and uric acid) were measured, as well as unchanged adenosine. Apparent uptake of adenosine was determined; it increased linearly with the concentration of adenosine infused. Adenosine was predominantly deaminated, even at low (1 mumol X litre-1) concentration. The inhibitory capacity of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was determined, while 5 mumol X litre-1 adenosine was infused. EHNA inhibited the apparent adenosine deaminase activity for 62 and 92% at 5 and 50 mumol X litre-1, respectively. When 50 mumol X litre-1 EHNA was infused into normoxic hearts, release of adenosine was significantly elevated, as was coronary flow. Induction of ischaemia increased total purine release four-to fivefold. Infusion of EHNA into ischaemic hearts did not alter total purine release, but adenosine release increased from 15 to 60% of total purines. However, when EHNA was present, a large part of total purine release still existed of inosine, hypoxanthine, xanthiner and uric acid. This was 83% during normoxia and 40% during ischaemia. These results suggest significant contribution of IMP and GMP breakdown to purine release from isolated perfused rat hearts.
定量测定心肌腺苷的生成和分解对于深入了解其生理作用的机制和调节至关重要。通过灌注腺苷（1至20 μmol·L⁻¹），研究了离体灌注大鼠心脏中腺苷的脱氨作用。测定了灌注液中的所有代谢产物（肌苷、次黄嘌呤、黄嘌呤和尿酸）以及未改变的腺苷。测定了腺苷的表观摄取量；其随灌注腺苷浓度呈线性增加。即使在低浓度（1 μmol·L⁻¹）下，腺苷也主要发生脱氨作用。在灌注5 μmol·L⁻¹腺苷时，测定了腺苷脱氨酶抑制剂erythro - 9-(2 - 羟基 - 3 - 壬基)腺嘌呤（EHNA）的抑制能力。EHNA在5和50 μmol·L⁻¹时分别抑制表观腺苷脱氨酶活性62%和92%。当向正常氧合心脏灌注50 μmol·L⁻¹ EHNA时，腺苷释放显著升高，冠状动脉血流量也显著升高。缺血诱导使总嘌呤释放增加四至五倍。向缺血心脏灌注EHNA并未改变总嘌呤释放，但腺苷释放从总嘌呤的15%增加到60%。然而，当存在EHNA时，总嘌呤释放的很大一部分仍然是肌苷、次黄嘌呤、黄嘌呤和尿酸。在正常氧合时这一比例为83%，缺血时为40%。这些结果表明，肌苷酸和鸟苷酸的分解对离体灌注大鼠心脏中嘌呤释放有显著贡献。
