Scotini E, Carpenedo F, Fassina G
Pharmacol Res Commun. 1983 Feb;15(2):131-43. doi: 10.1016/s0031-6989(83)80055-1.
The effects of some old and new methylxanthines and 6-thioxanthines, i.e. theophylline (TH), caffeine (CAFF), thiotheophyl line (S-TH), thiocaffeine (S-CAFF), 8-phenyltheophylline (8-PT), 3-isobutyl-1-methyl-xanthine (IBMX) were compared at the level of adipose tissue on spontaneous and norepinephrine-induced lipolysis as well as on fat cell phosphodiesterases. These agents stimulated lipolysis. 8-PT was the most potent; thiocaffeine and thiotheophylline the least potent; IBMX and theophylline had intermediate potencies. The order of potency of the same drugs in potentiating norepinephrine-stimulated lipolysis was: IBMX greater than 8-PT greater than S-CAFF greater than greater than S-TH greater than CAFF greater than TH. The rank order of potency to inhibit cAMP phosphodiesterases was: IBMX greater than S-TH and S-CAFF greater than TH much greater than 8-PT (uneffective). Thus (a) thiocaffeine and thiotheophylline were more potent than the parent compound theophylline in inhibiting cAMP-PDE, although their per se stimulating effect on lipolysis was much lower. This indicates that in the thioxanthines the stimulus per se on lipolysis can be dissociated from their effectiveness as inhibitors of PDE. (b) In contrast, 8-PT (a blocker of adenosine receptors) has a potent lipolytic action per se and a potentiating effect on norepinephrine-induced lipolysis, even if deprived of effect on PDE. This indicates that the potentiating power of methylxanthines on norepinephrine-stimulated lipolysis is not strictly dependent on their anti-PDE activities. These results suggest that in adipose tissue (more similar than adipocytes to the in vivo conditions) the anti-adenosine potency of methylxanthines is the prominent factor in stimulating basal lipolysis. Both anti-adenosine and anti-PDE activities are involved in modulating hormone-induced lipolysis.
比较了一些新旧甲基黄嘌呤和6-硫代黄嘌呤，即茶碱（TH）、咖啡因（CAFF）、硫代茶碱（S-TH）、硫代咖啡因（S-CAFF）、8-苯基茶碱（8-PT）、3-异丁基-1-甲基黄嘌呤（IBMX）在脂肪组织水平上对自发和去甲肾上腺素诱导的脂肪分解以及对脂肪细胞磷酸二酯酶的影响。这些药物刺激了脂肪分解。8-PT作用最强；硫代咖啡因和硫代茶碱作用最弱；IBMX和茶碱作用强度居中。相同药物增强去甲肾上腺素刺激的脂肪分解的效力顺序为：IBMX＞8-PT＞S-CAFF＞＞S-TH＞CAFF＞TH。抑制环磷酸腺苷磷酸二酯酶的效力顺序为：IBMX＞S-TH和S-CAFF＞TH＞＞8-PT（无作用）。因此，（a）硫代咖啡因和硫代茶碱在抑制环磷酸腺苷磷酸二酯酶方面比母体化合物茶碱更有效，尽管它们本身对脂肪分解的刺激作用要低得多。这表明在硫代黄嘌呤中，对脂肪分解的刺激本身可以与其作为磷酸二酯酶抑制剂的有效性相分离。（b）相反，8-PT（一种腺苷受体阻滞剂）本身具有强大的脂肪分解作用，并且对去甲肾上腺素诱导的脂肪分解有增强作用，即使对磷酸二酯酶没有作用。这表明甲基黄嘌呤对去甲肾上腺素刺激的脂肪分解的增强作用并不严格依赖于它们的抗磷酸二酯酶活性。这些结果表明，在脂肪组织中（比脂肪细胞更类似于体内情况），甲基黄嘌呤的抗腺苷效力是刺激基础脂肪分解的主要因素。抗腺苷和抗磷酸二酯酶活性都参与调节激素诱导的脂肪分解。
