Shim C, Lee D K, Lee C C, Cho W K, Kim K
Department of Molecular Biology, College of Natural Sciences, Seoul National University, Korea.
Mol Reprod Dev. 1992 Apr;31(4):280-6. doi: 10.1002/mrd.1080310409.
The potential action of purines, such as hypoxanthine and adenosine, in meiotic arrest was examined using denuded mouse oocytes. The spontaneous meiotic maturation of denuded oocytes was significantly inhibited by hypoxanthine and/or adenosine in a dose-dependent manner. Germinal vesicle breakdown (GVBD) was inhibited even at a low concentration (1 nM) of hypoxanthine, when hypoxanthine was microinjected into the cytoplasm of denuded oocytes. This inhibitory action was potentiated by co-injection with allopurinol, a metabolic blocker of hypoxanthine that can block a metabolic pathway to uric acid. By contrast, a microinjection of adenosine was no longer effective in inhibiting GVBD. Inhibitory action of purines in meiotic maturation was correlated with sustaining intracellular cAMP levels. GVBD was resumed by econazole, one of the nitroimidazole derivatives which act as inhibitors of catalytic subunit of adenylate cyclase. This compound was effective in counteracting the effect of adenosine, but not the action of 3-isobutyl-1-methylxanthine (IBMX) on GVBD, indicating that adenosine is probably exerted at the level of oocyte plasmalemma. These data suggest that the inhibitory action of hypoxanthine and adenosine in oocyte meiotic maturation may be involved in the regulation of cAMP metabolism in a differential manner.
利用去透明带小鼠卵母细胞研究了嘌呤(如次黄嘌呤和腺苷)在减数分裂阻滞中的潜在作用。次黄嘌呤和/或腺苷以剂量依赖的方式显著抑制了去透明带卵母细胞的自发减数分裂成熟。当将次黄嘌呤显微注射到去透明带卵母细胞的细胞质中时,即使在低浓度(1 nM)下,生发泡破裂(GVBD)也受到抑制。与次黄嘌呤的代谢阻滞剂别嘌呤醇共同注射可增强这种抑制作用,别嘌呤醇可阻断生成尿酸的代谢途径。相比之下,显微注射腺苷对抑制GVBD不再有效。嘌呤在减数分裂成熟中的抑制作用与维持细胞内cAMP水平相关。通过益康唑恢复了GVBD,益康唑是一种硝基咪唑衍生物,可作为腺苷酸环化酶催化亚基的抑制剂。该化合物可有效抵消腺苷的作用,但对3-异丁基-1-甲基黄嘌呤(IBMX)对GVBD的作用无效,这表明腺苷可能作用于卵母细胞质膜水平。这些数据表明,次黄嘌呤和腺苷在卵母细胞减数分裂成熟中的抑制作用可能以不同方式参与cAMP代谢的调节。