Kim J K, Jackson B A, Edwards R M, Dousa T P
J Lab Clin Med. 1982 Jan;99(1):29-38.
The effects of PDN on VP-sensitive cAMP metabolism were examined in MCT and MAL microdissected from the rat kidney. VP-sensitive adenylate cyclase activity was significantly reduced (delta -46%; p less than 0.05) in MAL of PDN rats but, in sharp contrast, was significantly increased (delta +79%; p less than 0.02) in MCT of PDN rats compared to controls. cAMP phosphodiesterase activity was significantly increased in both MAL (delta +59%; p less than 0.005) and MCT (delta +79%; p less than 0.001) of PDN rats compared to controls. The increase in cAMP accumulation in MAL measured in response to VP in intact tubules did not differ between PDN and controls, whereas cAMP accumulation in response to VP was significantly higher (delta +127%; p less than 0.001) in MCT of PDN rats compared to controls. The present results would indicate that the observed in vivo resistance to the antidiuretic effect of VP that occurs in PDN is not due to an impairment in VP-sensitive cAMP accumulation in MCT, but would rather suggest that a defect exists at a cellular step subsequent to cAMP generation. In addition, our results illustrate that the extent and directionality of in situ accumulation of cAMP measured in intact tubules cannot always be predicted from rhe activities of enzymes controlling its synthesis and degradation (adenylate cyclase and cAMP phosphodiesterase), which are measured in vitro in disrupted tubules.
在从大鼠肾脏显微分离出的髓质集合管（MCT）和髓质升支粗段（MAL）中检测了去甲丙咪嗪（PDN）对血管加压素（VP）敏感的环磷酸腺苷（cAMP）代谢的影响。与对照组相比，PDN大鼠的MAL中对VP敏感的腺苷酸环化酶活性显著降低（降低46%；p<0.05），但与之形成鲜明对比的是，PDN大鼠的MCT中该活性显著增加（增加79%；p<0.02）。与对照组相比，PDN大鼠的MAL（增加59%；p<0.005）和MCT（增加79%；p<0.001）中的cAMP磷酸二酯酶活性均显著增加。在完整肾小管中，PDN组和对照组对VP反应时MAL中cAMP积累的增加没有差异，而与对照组相比，PDN大鼠MCT中对VP反应时的cAMP积累显著更高（增加127%；p<0.001）。目前的结果表明，PDN大鼠体内观察到的对VP抗利尿作用的抵抗并非由于MCT中对VP敏感的cAMP积累受损，而是提示在cAMP生成后的细胞步骤存在缺陷。此外，我们的结果表明，在完整肾小管中测量的cAMP原位积累的程度和方向性不能总是从在破裂肾小管中体外测量的控制其合成和降解的酶（腺苷酸环化酶和cAMP磷酸二酯酶）的活性来预测。
