Oetjen E, Schweickhardt C, Unthan-Fechner K, Probst I
Institut für Biochemie, Georg-August Universität, Göttingen, Federal Republic of Germany.
Biochem J. 1990 Oct 15;271(2):337-44. doi: 10.1042/bj2710337.
The glycogenolytic potency of adenosine and ATP was studied in adult rat hepatocytes and compared with the action of glucagon and noradrenaline. In cells cultured for 48 h, adenosine and ATP as well as their analogues 2-chloroadenosine, phenylisopropyladenosine, N-ethylcarboxamidoadenosine and beta-gamma-methylene-substituted ATP (p[CH2]ppA) increased glycogen phosphorylase alpha to levels indistinguishable from those obtained by the addition of glucagon or noradrenaline. The P1 receptor antagonist 8-phenyltheophylline abolished the activation of phosphorylase by adenosine and by p[CH2]ppA, but not that by ATP. Protein kinase A was activated by p[CH2]ppA and ATP via their breakdown to adenosine. [14C]Glucose production from glycogen was stimulated only 3-fold by ATP and adenosine, compared with a 7-fold increase produced by the hormones. Stimulation of glucose production by glucagon or noradrenaline was almost completely abolished by ATP or adenosine, with half-maximal effects at around 10 microM. The non-degradable adenosine analogues were equipotent with glucagon with respect to stimulation of glucose production, and their action was also inhibited by adenosine. ATP and p[CH2]ppA, which were both degraded to adenosine, showed comparable metabolic effects, whereas the alpha, beta-methylene analogue was without biological action and also was not degraded to adenosine. In the presence of the adenosine transport inhibitor nitrobenzyl thioinosine (NBTI), adenosine exerted an increased glycogenolytic potency, reaching 80% of the maximal stimulation obtained by glucagon. The glucagon-antagonistic effect of adenosine could be completely abolished by NBTI, but was not affected by phenyltheophylline. It is concluded that, in the hepatocyte culture system, adenosine and ATP decrease the catalytic efficiency of phosphorylase alpha through signals arising from their uptake into the cell.
在成年大鼠肝细胞中研究了腺苷和ATP的糖原分解能力，并与胰高血糖素和去甲肾上腺素的作用进行了比较。在培养48小时的细胞中，腺苷和ATP及其类似物2-氯腺苷、苯异丙基腺苷、N-乙基羧酰胺腺苷和β-γ-亚甲基取代的ATP（p[CH2]ppA）可使糖原磷酸化酶α增加到与添加胰高血糖素或去甲肾上腺素时获得的水平无法区分的程度。P1受体拮抗剂8-苯基茶碱可消除腺苷和p[CH2]ppA对磷酸化酶的激活作用，但不能消除ATP对其的激活作用。蛋白激酶A通过p[CH2]ppA和ATP分解为腺苷而被激活。与激素引起的7倍增加相比，ATP和腺苷仅能刺激糖原产生的[14C]葡萄糖增加3倍。ATP或腺苷几乎完全消除了胰高血糖素或去甲肾上腺素对葡萄糖产生的刺激作用，在约10μM时产生半数最大效应。不可降解的腺苷类似物在刺激葡萄糖产生方面与胰高血糖素等效，并且它们的作用也受到腺苷的抑制。ATP和p[CH2]ppA都降解为腺苷，显示出相当的代谢效应，而α，β-亚甲基类似物没有生物学作用，也不会降解为腺苷。在腺苷转运抑制剂硝基苄基硫代肌苷（NBTI）存在的情况下，腺苷发挥出增强的糖原分解能力，达到胰高血糖素最大刺激作用的80%。腺苷的胰高血糖素拮抗作用可被NBTI完全消除，但不受苯基茶碱影响。得出的结论是，在肝细胞培养系统中，腺苷和ATP通过它们被细胞摄取所产生的信号降低了磷酸化酶α的催化效率。
