NITRIC-OXIDE ACTIVATES GUANYLATE CYCLASE AND INCREASES GUANOSINE 3'-5'-CYCLIC MONOPHOSPHATE LEVELS IN VARIOUS TISSUE PREPARATIONS
NITRIC-OXIDE ACTIVATES GUANYLATE CYCLASE AND INCREASES GUANOSINE 3'-5'-CYCLIC MONOPHOSPHATE LEVELS IN VARIOUS TISSUE PREPARATIONS
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DOI：
10.1073/pnas.74.8.3203
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发表时间：
1977-01-01
影响因子：
11.1
通讯作者：
MURAD, F
中科院分区：
文献类型：
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作者：
ARNOLD, WP;MITTAL, CK;MURAD, F
一氧化氮气体（NO）增加鸟苷酸环化酶[GTP焦磷酸裂解酶（环化），EC 4.6.1.2]在各种组织的可溶性和颗粒制剂中的活性。该效应具有剂量依赖性，并在检查的所有组织制备物中观察到。激活的程度是不同的组织制剂之间的变化，是最大的（19- 33倍）与肝，肺，气管平滑肌，心脏，肾脏，大脑皮层和小脑匀浆的上清液组分。在骨骼肌、脾、肠肌、肾上腺和附睾脂肪的上清液组分中观察到较小的影响（5- 14倍）。活化也观察到与部分纯化的制备鸟苷酸环化酶。激活大鼠肝上清液制剂略有增加与还原剂，减少与一些氧化剂，和更大的氮比在氧气气氛中。用NO激活后，鸟苷酸环化酶活性在4.0 ℃下以3-4小时的半衰期下降。C，但再次暴露于NO导致重新激活的准备工作。叠氮化钠，亚硝酸钠，羟胺和硝普钠也增加鸟苷酸环化酶的活性，如前所述。NO单独和与这些药剂组合产生大约相同程度的最大激活，表明所有这些药剂通过类似的机制起作用。NO也增加了环GMP的积累，但不从各种大鼠组织的切碎物孵育环AMP。各种硝基化合物和那些能够在孵育中形成NO的化合物通过类似但未定义的机制激活鸟苷酸环化酶。这些效应可以解释鸟苷酸环化酶在某些组织中的高活性（例如，肺和肠粘膜）暴露于环境硝基化合物。
Nitric oxide gas (NO) increased guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue preparations examined. The extent of activation was variable among different tissue preparations and was greatest (19- to 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex and cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal muscle, adrenal and epididymal fat. Activation was also observed with partially purified preparations of guanylate cyclase. Activation of rat liver supernatant preparations was augmented slightly with reducing agents, decreased with some oxidizing agents, and greater in a nitrogen than in an oxygen atmosphere. After activation with NO, guanylate cyclase activity decreased with a half-life of 3-4 h at 4.degree. C but reexposure to NO resulted in reactivation of preparations. Sodium azide, sodium nitrite, hydroxylamine and sodium nitroprusside also increased guanylate cyclase activity as reported previously. NO alone and in combination with these agents produced approximately the same degree of maximal activation, suggesting that all of these agents act through a similar mechanism. NO also increased the accumulation of cyclic GMP but not cyclic AMP in incubations of minces from various rat tissues. Various nitro compounds and those capable of forming NO in incubations activate guanylate cyclase through a similar but undefined mechanism. These effects may explain the high activities of guanylate cyclase in certain tissues (e.g., lung and intestinal mucosa) that are exposed to environmental nitro compounds.