Estey S J, Mansour T E
Department of Pharmacology, Stanford University School of Medicine, CA 94305.
Mol Biochem Parasitol. 1988 Jul;30(1):67-75. doi: 10.1016/0166-6851(88)90133-8.
Serotonin-stimulated adenylate cyclase activity in the trematode parasite Schistosoma mansoni increases 40-50-fold during its development from newly transformed schistosomulum to adult. The role of GTP in activation of the enzyme at different stages of development was investigated. Adenylate cyclase can be activated by the non-hydrolyzable GTP analogs 5'-guanylylimidodiphosphate (GppNHp) and guanosine-5'-(3-O-thiotriphosphate) (GTP gamma S), as well as by sodium fluoride. Activation by GTP gamma S is competitively antagonized by GTP. Cholera toxin catalyzes the ADP-ribosylation of several proteins in both early schistosomula and adults. Proteins of 93 and 53 kDa are labeled in both stages, but the other proteins labeled appear to be different in the two stages. Adult schistosomes exhibit autoribosylation by cholera toxin in a broad band at 41 kDa, and this is not seen in schistosomula. The effect of cholera toxin on cyclase activity was to reduce activation by serotonin, GTP gamma S, and fluoride, all agents which act through the GTP binding protein. Cholera toxin treatment also inhibits activation by optimal levels of forskolin, a diterpene that acts at the catalytic subunit. Pertussis toxin had little effect on cyclase activity, although it catalyzed the ADP-ribosylation of a single protein band at 45 kDa in both stages. The results suggest that the GTP binding protein that mediates adenylate cyclase activation by serotonin is somewhat different from Gs in the adrenergic adenylate cyclase system. The pertussis toxin substrate in S. mansoni does not appear to function as Gi.(ABSTRACT TRUNCATED AT 250 WORDS)
在曼氏血吸虫这种吸虫寄生虫中，血清素刺激的腺苷酸环化酶活性在其从新转化的童虫发育为成虫的过程中增加40至50倍。研究了GTP在发育不同阶段对该酶激活的作用。腺苷酸环化酶可被不可水解的GTP类似物5'-鸟苷酰亚胺二磷酸（GppNHp）和鸟苷-5'-(3-O-硫代三磷酸)（GTPγS）以及氟化钠激活。GTPγS的激活作用受到GTP的竞争性拮抗。霍乱毒素催化早期童虫和成虫中几种蛋白质的ADP核糖基化。在两个阶段中，93 kDa和53 kDa的蛋白质都被标记，但两个阶段中其他被标记的蛋白质似乎不同。成虫血吸虫在41 kDa处有一条宽条带显示霍乱毒素的自身核糖基化，而在童虫中未观察到。霍乱毒素对环化酶活性的影响是降低血清素、GTPγS和氟化物的激活作用，所有这些试剂都是通过GTP结合蛋白起作用的。霍乱毒素处理也抑制了最佳水平的福斯可林（一种作用于催化亚基的二萜）的激活作用。百日咳毒素对环化酶活性影响很小，尽管它在两个阶段都催化了一条45 kDa单蛋白条带的ADP核糖基化。结果表明，介导血清素激活腺苷酸环化酶的GTP结合蛋白与肾上腺素能腺苷酸环化酶系统中的Gs有所不同。曼氏血吸虫中的百日咳毒素底物似乎不发挥Gi的作用。（摘要截短至250字）
