THE ROLE OF CYCLIC-NUCLEOTIDES IN ATRIAL NATRIURETIC PEPTIDE-MEDIATED INHIBITION OF ALDOSTERONE SECRETION
THE ROLE OF CYCLIC-NUCLEOTIDES IN ATRIAL NATRIURETIC PEPTIDE-MEDIATED INHIBITION OF ALDOSTERONE SECRETION
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DOI：
10.1210/endo-122-3-799
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发表时间：
1988-03-01
期刊：
影响因子：
4.8
通讯作者：
ISALES, CM
中科院分区：
文献类型：
--
作者：
BARRETT, PQ;ISALES, CM
使用新鲜分离的牛肾上腺肾小球细胞，我们检查了心房钠素（ANP）对使用Ca2+-磷酸肌肽或cAMP信使系统的激动剂刺激的醛固酮分泌的抑制作用。在连续灌注系统中，血管紧张素II （AII）诱导醛固酮分泌迅速上升，随后持续分泌反应。这两个阶段的分泌都被ANP迅速和独立地抑制。两个环核苷酸，cGMP和cAMP，作为这种anp诱导的抑制的介质的作用进行了研究。8-溴- cgmp (1-100 .mu。M)或（Bu）2cGMP （1-50 .mu）。M)在浸润系统中研究了aii刺激的分泌速率。这两种类似物，无论是早期添加还是后期添加，最大限度地抑制20-30%的醛固酮分泌，仅在后期或持续阶段。在静态培养系统中检测了ANP对细胞cAMP含量的影响。虽然ANP引起AII或ACTH刺激的细胞cAMP含量降低，但它对乙醇刺激的细胞cAMP水平几乎没有影响。在AII-和acth刺激的细胞中，探讨了cAMP含量降低与分泌减少之间的关系。在ANP抑制的aii刺激细胞中，单纯用forskolin恢复cAMP含量并不能恢复分泌速率。百日咳毒素处理阻断了ANP对cAMP含量的抑制作用，但未阻断其对cAMP分泌的抑制作用。在ACTH刺激的细胞中，用福斯可林逆转ANP诱导的cAMP的减少，部分恢复了受刺激的分泌速率，尽管在ANP存在的情况下，用10倍高剂量的ACTH恢复cAMP并没有恢复受刺激的分泌速率。这些结果表明，anp诱导的cGMP升高和anp诱导的细胞cAMP含量降低可能有助于抑制甾体生成。然而，这些抑制信息不会诱导ANP诱导的抑制的幅度或时间模式。因此，肾上腺多信使系统可能是ANP作用的基础。
Using freshly isolated bovine adrenal glomerulosa cells we examined the inhibitory effect of atrial natriuretic peptide (ANP) on aldosterone secretion stimulated by agonists that use either the Ca2+-phosphoinositide or cAMP messenger system. In a continuous perifusion system, angiotensin II (AII) induces a prompt initial rise in aldosterone secretion, followed by a sustained secretory response. Both phases of secretion are rapidly and idependently inhibited by ANP. The role of two cyclic nucleotides, cGMP and cAMP, as mediators of this ANP-induced inhibition was examined. The effect of 8-bromo-cGMP (1-100 .mu.M) or (Bu)2cGMP (1-50 .mu.M) on the AII-stimulated rate of secretion was studied in a perifusion system. Either analog, whether added early or late, maximally inhibited by 20-30% only the late or sustained phase of aldosterone secretion. The effect of ANP on cellular cAMP content was examined in a static incubation system. Although ANP caused a reduction in the cAMP content of cells stimulated with either AII or ACTH, it had little or no effect on the cAMP levels in cells stimulated with carbachol. In AII- and ACTH-stimulated cells, the relationship between reduced cAMP content and reduced secretion was explored. In the AII-stimulated cell inhibited by ANP, simple restoration of cAMP content with forskolin did not restore the secretory rate. Pertussis toxin treatment blocked the inhibitory effect of ANP on cAMP content, but did not block its inhibition of secretion. In the ACTH-stimulated cell, reversal of the ANP-induced reduction of cAMP with forskolin, partially restored the stimulated rate of secretion, although restoration of cAMP with a 10-fold higher dose of ACTH did not restore the stimulated rate of secretion in the presence of ANP. These results imply that both the ANP-induced rise in cGMP and the ANP-induced decrease in cellular cAMP content may contribute to the inhibition of steroidogenesis. However, these inhibitory messages do not induce either the magnitude or the temporal pattern of inhibition induced by ANP. Thus, in the adrenal multiple messenger systems may underlie the action of ANP.