Effects of Epinephrine, Adrenocorticotrophic Hormone, and Theophylline on Adenosine 3′,5′-Monophosphate Phosphodiesterase Activity in Fat Cells

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RESUMO

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 μM) in the 100,000 × 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.

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