Tremblay J, Gerzer R, Vinay P, Pang S C, Béliveau R, Hamet P
FEBS Lett. 1985 Feb 11;181(1):17-22. doi: 10.1016/0014-5793(85)81105-4.
We have demonstrated previously that atrial natriuretic factor (ANF) augments urinary, plasma and kidney cGMP levels but has no significant effect upon cAMP. Using cGMP as a marker, we searched for specific target sites involved in the action of ANF in the dog kidney, and observed no change of cGMP in the proximal tubules, a 2-fold increase over basal levels in the thick loop of Henle and a 3-fold elevation in the collecting duct. The most striking action on cGMP occurred in the glomeruli with a rise of up to 50-fold being evident at 1-2 min. after the addition of ANF. The results obtained in the absence or presence of a phosphodiesterase inhibitor support the notion that the effects of ANF were exerted at the level of guanylate cyclase stimulation rather than cGMP phosphodiesterase inhibition. The action of sodium nitroprusside (SNP), a direct stimulator of soluble guanylate cyclase, differed from that of ANF. The ability of the factor to enhance cGMP levels was correlated with the distribution of particulate guanylate cyclase. This study identifies the glomeruli and the distal part of the nephron as specific targets of ANF and implicates particulate guanylate cyclase as the enzyme targetted for the expression of its action.
我们先前已经证明，心房利钠因子（ANF）可提高尿液、血浆和肾脏中的环鸟苷酸（cGMP）水平，但对环磷酸腺苷（cAMP）没有显著影响。以cGMP作为标志物，我们在犬肾中寻找参与ANF作用的特定靶位点，结果发现近端小管中的cGMP没有变化，髓袢升支粗段中的cGMP比基础水平增加了2倍，集合管中的cGMP升高了3倍。对cGMP最显著的作用发生在肾小球，添加ANF后1 - 2分钟内，cGMP明显升高至50倍。在存在或不存在磷酸二酯酶抑制剂的情况下获得的结果支持了这样一种观点，即ANF的作用是在鸟苷酸环化酶刺激水平上发挥的，而不是通过抑制cGMP磷酸二酯酶。硝普钠（SNP）作为可溶性鸟苷酸环化酶的直接刺激剂，其作用与ANF不同。该因子提高cGMP水平的能力与颗粒性鸟苷酸环化酶的分布相关。这项研究确定肾小球和肾单位的远端部分是ANF的特定靶标，并表明颗粒性鸟苷酸环化酶是其作用表达的酶靶标。
