ADENOSINE-DEAMINASE INHIBITION AND MYOCARDIAL PURINE RELEASE DURING NORMOXIA AND ISCHEMIA
ADENOSINE-DEAMINASE INHIBITION AND MYOCARDIAL PURINE RELEASE DURING NORMOXIA AND ISCHEMIA
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DOI：
10.1093/cvr/19.10.593
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发表时间：
1985-01-01
影响因子：
10.8
通讯作者：
DEJONG, JW
中科院分区：
文献类型：
--
作者：
ACHTERBERG, PW;HARMSEN, E;DEJONG, JW
定量测定心肌腺苷的形成和分解对于深入了解其生理作用的机制和调节是必要的。在离体灌流的大鼠心脏中，通过注入腺苷(1~20微克分子单位)来研究腺苷的脱氨作用。升-1)。测定灌流液中的所有分解代谢物(肌苷、次黄嘌呤、黄嘌呤和尿酸)，以及不变的腺苷。测定了腺苷的表观摄取量；它随着腺苷浓度的增加而线性增加。腺苷以脱氨基为主，即使在低浓度(1µmol.cntdo.升-1)浓度。测定了腺苷脱氨酶抑制剂赤藓-9-(2-羟基-3-壬基)腺嘌呤(EHNA)和5微克分子氰化钠的抑制能力。静注1升腺苷。EHNA对腺苷脱氨酶活性的抑制作用在5和50微克分子浓度时分别为62%和92%。升-1。当50微克分子碳纳米点时。向常氧心脏注入L-1EHNA后，腺苷的释放显著增加，冠脉流量也显著增加。诱导缺血使总纯释放量增加四到五倍。向缺血心脏中注入eHNA并不改变总的嘌呤释放量，但腺苷释放量从总嘌呤的15%增加到60%。然而，当EHNA存在时，很大一部分嘌呤的总释放仍然以肌苷、次黄嘌呤、黄嘌呤和尿酸的形式存在。这一比例在常氧时为83%，在缺血期为40%。这些结果表明，IMP和GMP的破坏对离体灌流大鼠心脏的嘌呤释放有重要贡献。
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 .mu.mol .cntdot. 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 .mu.mol .cntdot. litre-1) concentration. The inhibitory capacity of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was determined, while 5 .mu.mol .cntdot. litre-1 adenosine was infused. EHNA inhibited the apparent adenosine deaminase activity for 62 and 92% at 5 and 50 .mu.mol .cntdot. litre-1, respectively. When 50 .mu.mol .cntdot. litre-1 EHNA was infused into normoxic hearts, release of adenosine was significantly elevated, as was coronary flow. Induction of ischaemia increased total pure 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.