别嘌呤醇、红-9-(2-羟基-3-壬基)腺嘌呤和S-(4-硝基苄基)-6-硫代肌苷对大鼠结肠粘膜肌层5 ' -三磷酸腺苷降解的影响

J. P. Tennant, F. Callaghan, C. Turner, S. M. O. Hourani
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引用次数: 2

摘要

在大鼠结肠粘膜肌层中研究了一些腺苷转运或代谢调节剂对ATP分解的影响,该组织收缩为ATP,被认为含有P2Y1受体。实验化合物为黄嘌呤氧化酶抑制剂别嘌呤醇、腺苷脱氨酶抑制剂红-9-(2-羟基-3-壬基)腺嘌呤(EHNA)和腺苷摄取阻滞剂S-(4-硝基苄基)-6-硫代氨基苷(NBTI)。2在分离组织制剂单独孵育或与药物共孵育1小时后,用高压液相色谱法观察5 ' -三磷酸腺苷(ATP) (100 μm)的降解和代谢物的出现。3 .在没有药物的情况下,ATP在大鼠结肠粘膜肌层中被快速降解,半衰期为6.1±0.7 min,主要分解产物为肌苷而非腺苷。别嘌呤醇(1 μm)和NBTI (10 μm)对ATP的分解速率和代谢产物的生成模式没有影响。EHNA (1 μm或10 μm)对ATP的半衰期也没有影响,但在EHNA (1 μm)的存在下,肌苷的生成速率明显降低,并检测到一些腺苷,而在EHNA (10 μm)的存在下,肌苷的生成被消除,腺苷成为最终的分解产物。这些结果表明,别嘌呤醇(1 μm)和NBTI (10 μm)对该组织的细胞外嘌呤代谢没有可检测到的影响,并且EHNA处理产生的腺苷的积累对ATP分解没有反馈作用。
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Effects of allopurinol, erythro-9-(2-hydroxy-3-nonyl)adenine and S-(4-nitrobenzyl)-6-thioinosine on the degradation of adenosine 5′-triphosphate in the rat colon muscularis mucosae

1 The effects on ATP breakdown of some modulators of adenosine transport or metabolism were studied in the rat colon muscularis mucosae, a tissue which contracts to ATP and is thought to contain P2Y1 receptors. The compounds tested were the xanthine oxidase inhibitor allopurinol, the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and the adenosine uptake blocker S-(4-nitrobenzyl)-6-thioinosine (NBTI).

2 The degradation of adenosine 5′-triphosphate (ATP) (100 μm) and the appearance of metabolites was followed by high pressure liquid chromatography during incubation of isolated tissue preparations alone or in the presence of the drugs, following preincubation with the drugs for 1 h.

3 In the absence of drugs ATP was rapidly degraded by the rat colon muscularis mucosae with a half-life of 6.1 ± 0.7 min, the major breakdown product being inosine rather than adenosine. Allopurinol (1 μm) and NBTI (10 μm) had no effect on the rate of breakdown of ATP or on the pattern of metabolites produced. EHNA (1 or 10 μm) also had no effect on the half-life of ATP, but in the presence of EHNA (1 μm) the rate of production of inosine was significantly reduced and some adenosine was detected, while in the presence of 10 μm EHNA the production of inosine was abolished and adenosine became the final breakdown product.

4 These results indicate that allopurinol (1 μm) and NBTI (10 μm) have no detectable effect on extracellular purine metabolism in this tissue, and that the build-up of adenosine produced by treatment with EHNA does not have a feedback effect on ATP breakdown.

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Issue Information Autonomic and Autacoid Pharmacology: Goodbye and thank you Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue Retraction: Dopamine receptor immunohistochemistry in the rat choroid plexus. Issue Information
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