Nishisaki H, Sakamoto C, Konda Y, Nakano O, Matozaki T, Nagao M, Matsuda K, Wada K, Kasuga M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Dig Dis Sci. 1992 Oct;37(10):1593-9. doi: 10.1007/BF01296507.
To better understand phosphatidylcholine synthesis in the stomach, we isolated guinea pig gastric glands and examined their [3H]choline incorporation into phosphatidylcholine in response to either antiulcer drugs such as geranylgeranylacetone (GGA) and H2-receptor antagonists or agents that cause phosphatidylcholine synthesis in other tissues. [3H]Choline incorporation was stimulated by GGA, palmitate, and 12-O-tetradecanoylphorbol-13-acetate (TPA). Dibutyryl cyclic-AMP had no effect. By contrast with GGA, famotidine, ranitidine, and cimetidine equipotently inhibited [3H]choline incorporation into phosphatidylcholine. GGA, palmitate, and TPA increased phosphatidyl-[3H]choline and decreased phosphoryl-[3H]choline as compared with control in tissues that had been pulsed with [3H]choline. On the other hand, no more decrease in [3H]choline incorporation at chase periods was observed in pulse-labeled glands in response to each H2-receptor antagonist. The particulate fraction of glands that had been incubated with GGA or palmitate had more CTP-phosphocholine cytidylyltransferase activity than that of glands incubated without agents. A decrease in choline kinase activity was not observed in the cytosolic fraction of glands that had been incubated with cimetidine. These results suggest that GGA and palmitate stimulate phosphatidylcholine synthesis by activating cytidylyltransferase, and H2-receptor antagonists may affect phosphatidylcholine synthesis by inhibiting choline uptake in the gastric glands.
为了更好地理解胃中磷脂酰胆碱的合成过程，我们分离了豚鼠胃腺，并检测了它们在抗溃疡药物（如香叶基香叶基丙酮（GGA）和H2受体拮抗剂）或能在其他组织中引发磷脂酰胆碱合成的试剂作用下，[3H]胆碱掺入磷脂酰胆碱的情况。GGA、棕榈酸酯和12-O-十四酰佛波醇-13-乙酸酯（TPA）刺激了[3H]胆碱的掺入。二丁酰环磷腺苷没有作用。与GGA相反，法莫替丁、雷尼替丁和西咪替丁等效抑制了[3H]胆碱掺入磷脂酰胆碱。与用[3H]胆碱脉冲处理过的组织中的对照相比，GGA、棕榈酸酯和TPA增加了磷脂酰-[3H]胆碱并减少了磷酸-[3H]胆碱。另一方面，在脉冲标记的腺体中，对每种H2受体拮抗剂的反应在追踪期未观察到[3H]胆碱掺入的进一步减少。用GGA或棕榈酸酯孵育过的腺体的微粒部分比未用试剂孵育的腺体具有更高的CTP-磷酸胆碱胞苷转移酶活性。在用西咪替丁孵育过的腺体的胞质部分未观察到胆碱激酶活性的降低。这些结果表明，GGA和棕榈酸酯通过激活胞苷转移酶来刺激磷脂酰胆碱的合成，而H2受体拮抗剂可能通过抑制胃腺中胆碱的摄取来影响磷脂酰胆碱的合成。
