DeRubertis F R, Zenser T V, Craven P A, Davis B B
J Clin Invest. 1976 Dec;58(6):1370-8. doi: 10.1172/JCI108592.
The lower O2 tension and more active anerobic metabolism that pertain in the inner medulla (IM) of kidney relative to cortex (C) are well recognized, but there is no evidence that O2 availability constitutes a limiting or regulatory factor in IM metabolism or function. In the present in vitro study, we examined the effects of O2 on adenosine 3',5'-monophosphate (cAMP) metabolism in slices of rat renal C and IM. After a 20-min incubation of slices in Krebs Ringer bicarbonate buffer with 95% O2 + 5% CO2 serving as the gas phase, the cAMP content of IM was 6-10 fold higher than that of C in either the presence or absence of 2 mM 1-methyl-3-isobutylxanthine in the incubation media. In slices of IM incubated for 20 min with 1-methyl-3-isobutylxanthine, cAMP was 22.5+/-SE 2.48 pmol/mg wet weight at 95% O2 and 4.37 without O2. Oxygenation of O2-deprived IM increased cAMP twofold in 2 min, an effect fully expressed in 5 min (fivefold increase). Further, cAMP of IM rose progressively and significantly over a range of atmospheric O2 content from 0 to 50% conditions which should reproduce and encompass O2 tensions that pertain in tissues in vivo. By contrast, basal cAMP content of C varied less than twofold in the presence of 95% versus no O2, implying that O2 modulation of cAMP was specific for IM. Indomethacin and meclofenamate, structurally distinct inhibitors of prostaglandin synthesis, both significantly decreased basal cAMP accumulation in oxygenated slices of IM but not of C. Meclofenamate also reduced basal adenylate cyclase activity determined in homogenates prepared from slices of IM which had been incubated at 95% O2. In slices of IM previously exposed to indomethacin or meclofenamate at 95% O2, a maximally effective concentration of exogenous prostaglandin E1 restored cAMP and adenylate cyclase activity to levels which approximated those observed at 95% O2 in the absence of an inhibitor of prostaglandin synthesis. These results suggest that O2 enhancement of cAMP content in IM may be mediated at least in part by local prostaglandins.
相对于肾皮质（C）而言，肾髓质内层（IM）中较低的氧分压和更活跃的无氧代谢是广为人知的，但没有证据表明氧的可利用性构成IM代谢或功能的限制或调节因素。在本体外研究中，我们检测了氧对大鼠肾C和IM切片中3',5'-环磷酸腺苷（cAMP）代谢的影响。将切片在以95% O₂ + 5% CO₂作为气相的 Krebs-Ringer碳酸氢盐缓冲液中孵育20分钟后，无论孵育介质中是否存在2 mM 1-甲基-3-异丁基黄嘌呤，IM的cAMP含量都比C高6 - 10倍。在含有1-甲基-3-异丁基黄嘌呤的情况下，将IM切片孵育20分钟，在95% O₂时cAMP为22.5±标准误2.48 pmol/mg湿重，无氧时为4.37。对缺氧的IM进行氧合处理，2分钟内cAMP增加两倍，5分钟时达到完全效应（增加五倍）。此外，在大气氧含量从0到50%的范围内，IM的cAMP逐渐且显著升高，这些条件应能再现并涵盖体内组织中的氧分压情况。相比之下，在95% O₂与无氧条件下，C的基础cAMP含量变化不到两倍，这意味着氧对cAMP的调节对IM具有特异性。吲哚美辛和甲氯芬那酸是结构不同的前列腺素合成抑制剂，它们均显著降低了氧合的IM切片而非C切片中的基础cAMP积累。甲氯芬那酸还降低了由在95% O₂孵育的IM切片制备的匀浆中测定的基础腺苷酸环化酶活性。在先前于95% O₂暴露于吲哚美辛或甲氯芬那酸的IM切片中，最大有效浓度的外源性前列腺素E₁将cAMP和腺苷酸环化酶活性恢复到接近在不存在前列腺素合成抑制剂时95% O₂条件下观察到的水平。这些结果表明，氧对IM中cAMP含量的增强作用可能至少部分由局部前列腺素介导。
