Okumura T, Sago T, Saito K
Department of Medical Chemistry, Kansai Medical School, Osaka, Japan.
Biochim Biophys Acta. 1988 Feb 4;958(2):179-87. doi: 10.1016/0005-2760(88)90175-0.
Hepatocytes were isolated by collagenase perfusion method from adult male rats, cultured and then prelabeled with [14C]glucose. The [14C]glycogen-labeled cells were used in experiments for effect of prostaglandins on hormone-stimulated glycogenolysis. Prostaglandin E1, prostaglandin E2 and 16,16-dimethylprostaglandin E2, but not prostaglandin D2 or prostaglandin F2 alpha, inhibited glycogenolysis stimulated by glucagon, epinephrine, isoproterenol (beta-adrenergic agonist) or epinephrine in the presence of propranolol (beta-antagonist) in primary cultured hepatocytes. The inhibitory effects on day 2 of cultures were approx. twice those on day 1. Dimethylprostaglandin E2 (10(-6)M) caused 60-70% inhibitions of the stimulations by these substances. In the case of the stimulation by glucagon, the inhibition further increased by 80-100% on day 3 of culture. Prostaglandin E1 and prostaglandin E2 caused less inhibition than dimethylprostaglandin E2 of all these stimulations. Dinorprostaglandin E1 (9 alpha,13-dihydroxy-7-ketodinorprost-11-enoic acid), which is a hepatocyte-metabolite of prostaglandin E1 and prostaglandin E2, and arachidonic acid did not have any inhibitory effects. These data indicate that the E series of prostaglandins may function as the regulation of hepatic glycogenolysis stimulated by epinephrine and glucagon, and that their rapid degradation system may contribute to the modulation of the action in liver.
采用胶原酶灌注法从成年雄性大鼠中分离肝细胞，进行培养，然后用[14C]葡萄糖进行预标记。将[14C]糖原标记的细胞用于实验，以研究前列腺素对激素刺激的糖原分解的影响。前列腺素E1、前列腺素E2和16,16-二甲基前列腺素E2可抑制原代培养肝细胞中胰高血糖素、肾上腺素、异丙肾上腺素（β-肾上腺素能激动剂）或在普萘洛尔（β-拮抗剂）存在下肾上腺素刺激的糖原分解，但前列腺素D2或前列腺素F2α则无此作用。培养第2天的抑制作用约为第1天的两倍。二甲基前列腺素E2（10(-6)M）可使这些物质刺激引起的糖原分解抑制60-70%。在胰高血糖素刺激的情况下，培养第3天抑制作用进一步增加80-100%。前列腺素E1和前列腺素E2对所有这些刺激的抑制作用均小于二甲基前列腺素E2。前列腺素E1和前列腺素E2的肝细胞代谢产物去甲前列腺素E1（9α,13-二羟基-7-酮去甲前列腺-11-烯酸）和花生四烯酸均无抑制作用。这些数据表明，前列腺素E系列可能在调节肾上腺素和胰高血糖素刺激的肝糖原分解中发挥作用，其快速降解系统可能有助于调节肝脏中的作用。
