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茶碱和二丁酰环磷酸腺苷在体内和体外的不同脂解作用。

Different lipolytic effects of theophylline and dibutyryl cyclic AMP in vivo and in vitro.

作者信息

Baum D, French J W

出版信息

Proc Soc Exp Biol Med. 1976 Feb;151(2):244-8. doi: 10.3181/00379727-151-39183.

DOI:10.3181/00379727-151-39183
PMID:175376
Abstract

Both dcAMP and theophylline are known to promote lipolysis in vitro by increasing intracellular cAMP. Although theophylline stimulates FFA mobilization in vivo as well, a report of low circulating FFA levels in the rat given dcAMP suggested that dcAMP may inhibit lipolysis in the intact animal. To explore this possibility, a comparison of the in vitro and in vivo lipolytic effects of theophylline and dcAMP was made in the young dog. Circulating glycerol and FFA levels rose following the administration of theophylline. While glycerol and FFA fell slightly in puppies given dcAMP, only the FFA change was significant. Epinephrine infusions given alone produced sustained elevations of glycerol and FFA. When theophylline was given in conjunction with ongoing epinephrine infusions, plasma glycerol and FFA levels remained high. On the other hand, epinephrine-stimulated lipolysis was markedly inhibited by dcAMP, as shown by pronounced falls of glycerol and FFA from the elevated levels found with epinephrine alone. In vitro studies involving fragments of puppy adipose tissue reveal that epinephrine, theophylline, and dcAMP promoted glycerol release. In contrast to the in vivo observations, lipolysis was also stimulated by combinations of both epinephrine and theophylline as well as by epinephrine and dcAMP. Thus, theophylline stimulates lipolysis in vitro and in vivo in the puppy. In contrast, dcAMP stimulates lipolysis in vitro but inhibits this action in the intact animal. This important difference in the two pharmacologic agents suggests the need for caution when using them in in vivo studies involving the action of cAMP.

摘要

已知双丁酰环磷腺苷(dcAMP)和茶碱都可通过增加细胞内环磷腺苷(cAMP)来促进体外脂肪分解。尽管茶碱在体内也能刺激游离脂肪酸(FFA)的动员,但有报告称,给大鼠注射dcAMP后其循环FFA水平较低,这表明dcAMP可能会抑制完整动物体内的脂肪分解。为探究这种可能性,研究人员在幼犬身上比较了茶碱和dcAMP的体外和体内脂肪分解作用。注射茶碱后,循环甘油和FFA水平升高。给幼犬注射dcAMP后,甘油和FFA略有下降,只有FFA的变化具有统计学意义。单独注射肾上腺素会使甘油和FFA持续升高。当在持续注射肾上腺素的同时注射茶碱时,血浆甘油和FFA水平仍然很高。另一方面,如单独注射肾上腺素后甘油和FFA水平升高,而注射dcAMP后甘油和FFA水平显著下降所示,dcAMP可显著抑制肾上腺素刺激的脂肪分解。涉及幼犬脂肪组织碎片的体外研究表明,肾上腺素、茶碱和dcAMP均可促进甘油释放。与体内观察结果相反,肾上腺素与茶碱的组合以及肾上腺素与dcAMP的组合也可刺激脂肪分解。因此,茶碱在幼犬体内外均可刺激脂肪分解。相比之下,dcAMP在体外可刺激脂肪分解,但在完整动物体内会抑制这种作用。这两种药物的这一重要差异表明,在涉及cAMP作用的体内研究中使用它们时需要谨慎。

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