期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1974
卷号：71
期号：5
页码：1639-1642
DOI：10.1073/pnas.71.5.1639
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：When rat fat cells were incubated with ACTH, epinephrine, or theophylline for 2 to 10 min, cyclic AMP phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, E.C. 3.1.4.17 ) activity (Km about 0.39 {micro}M) in the 100,000 x g sediment fraction of homogenates was increased 35 to 50%. The effects of epinephrine and ACTH were concentration dependent and maximal increases were produced with concentrations similar to those that maximally stimulate lipolysis. Theophylline (0.5 mM) similarly increased phosphodiesterase activity but did not enhance the effects of maximally effective concentrations of the hormones. The changes in phosphodiesterase activity following addition of ACTH or theophylline paralleled changes in cell cyclic AMP content; both reached a maximum within 5 min and then declined, approaching basal levels after 20 or 30 min. The increased phosphodiesterase activity in cells incubated for 5 min with epinephrine reverted to basal levels within 2.5 min after the addition of propranolol. Our data are consistent with the view that there is a component of the fat-cell phosphodiesterase, perhaps localized in the plasma membrane, whose activity can be acutely modified by the concentration of its substrate, cyclic AMP. As previously reported (J. Biol. Chem.248, 7164-7170, 1973), exposure of fat cells to insulin increases the activity of a low Km phosphodiesterase also localized in the 100,000 x g sediment fraction of fat cell homogenates. In the presence of insulin, however, phosphodiesterase remained elevated for at least 40 min and there was no significant change in fat-cell cyclic AMP content. When phosphodiesterase activity was elevated and cyclic AMP content maintained at a high level by incubation of cells with ACTH plus theophylline, insulin produced a further increase in enzyme activity. Whether or not insulin and ACTH (or epinephrine or theophylline) affect the same phosphodiesterase, there seems little doubt that the underlying mechanisms are different.
