Allen D O, Quesenberry J T
Department of Pharmacology, School of Medicine, University of South Carolina, Columbia.
J Pharmacol Exp Ther. 1988 Mar;244(3):852-8.
The relationships between cyclic AMP (cAMP) levels and glycerol release (lipolysis) were determined for isoproterenol and forskolin under varied conditions in the isolated fat cell of the rat. Prevention of the inhibitory action of endogenous adenosine [by adenosine deaminase (100 mU/ml) or theophylline (3.3 X 10(-4) M)] resulted in increased levels of cAMP and increased rates of lipolysis with forskolin. However, the relationship between cAMP levels and rates of lipolysis remained the same under all conditions. N6-phenylisopropyladenosine (PIA; an analog of adenosine) abolished the increase in cAMP level produced by isoproterenol (10(-7) M) or forskolin (10(-6) M) and the lipolytic response to forskolin. However, PIA failed to inhibit completely the lipolytic response to isoproterenol. Dose-response curves to isoproterenol were determined in the presence and absence of adenosine deaminase. PIA (10(-6) M) inhibited the increase in cAMP levels under both conditions. PIA also inhibited the lipolytic responses that were associated with increases in cAMP levels, i.e., high concentrations of isoproterenol alone and isoproterenol with adenosine deaminase. A plot of cAMP levels against corresponding rates of lipolysis for all conditions agreed with previous observations that the relationship for isoproterenol differs from that for forskolin. At any concentration of cAMP the corresponding lipolytic response was greater for isoproterenol than for forskolin. The possibility of a cAMP-independent lipolytic response was discussed.
在不同条件下，测定了大鼠分离脂肪细胞中异丙肾上腺素和福斯高林的环磷酸腺苷（cAMP）水平与甘油释放（脂解作用）之间的关系。通过腺苷脱氨酶（100 mU/ml）或茶碱（3.3×10⁻⁴ M）阻止内源性腺苷的抑制作用，可使福斯高林处理后的cAMP水平升高，脂解速率加快。然而，在所有条件下，cAMP水平与脂解速率之间的关系保持不变。N⁶-苯基异丙基腺苷（PIA；腺苷类似物）消除了异丙肾上腺素（10⁻⁷ M）或福斯高林（10⁻⁶ M）引起的cAMP水平升高以及对福斯高林的脂解反应。然而，PIA未能完全抑制对异丙肾上腺素的脂解反应。在有无腺苷脱氨酶存在的情况下，测定了对异丙肾上腺素的剂量反应曲线。PIA（10⁻⁶ M）在两种条件下均抑制cAMP水平的升高。PIA还抑制了与cAMP水平升高相关的脂解反应，即单独使用高浓度异丙肾上腺素以及异丙肾上腺素与腺苷脱氨酶共同作用时的脂解反应。所有条件下cAMP水平与相应脂解速率的关系图与先前的观察结果一致，即异丙肾上腺素与福斯高林的关系不同。在任何cAMP浓度下，异丙肾上腺素对应的脂解反应均大于福斯高林。文中讨论了存在不依赖cAMP的脂解反应的可能性。
