Nishikawa T, Yoshida A, Omura M, Sasano H, Noda M
Department of Medicine, Yokohama Rosai Hospital, Japan.
Endocr J. 1994 Oct;41(5):593-7. doi: 10.1507/endocrj.41.593.
It is well known that cholera toxin (CT) stimulates ADP-ribosylation of Gs and also pertussis toxin (PT) does Gi. Each GTP-binding protein has its own action in the regulation of adenylate cyclase. A human non-functioning adrenocortical cancer tissue showed an unresponsiveness in adenylate cyclase to ACTH although ACTH and CT activated adenylate cyclase in a non-functioning adrenal adenoma tissue. CT ADP-ribosylated 43 kDa protein of the plasma membrane of the cancer tissue while CT and PT could ADP-ribosylate 43 kDa and 38 kDa protein in the adenoma tissue, respectively. Immunoblotting analysis of the cancer tissue demonstrated that 40 kDa protein was detected by anti-Gs antibody as well as by anti-Gi antibody. The present experiments demonstrated that CT could ADP-ribosylate Gs which has stimulatory action on adenylate cyclase and also Gi which inhibits adenylate cyclase. Thus it is suggested that CT can activate the ADP-ribosylation of Gs and also Gi in a human adrenocortical cancer tissue, partly resulting in abnormal regulation of adenylate cyclase which may be crossly related to ACTH-unresponsiveness.
众所周知，霍乱毒素（CT）可刺激Gs的ADP核糖基化，百日咳毒素（PT）则可刺激Gi的ADP核糖基化。每种GTP结合蛋白在腺苷酸环化酶的调节中都有其自身的作用。一个人类无功能肾上腺皮质癌组织显示，腺苷酸环化酶对促肾上腺皮质激素（ACTH）无反应，尽管ACTH和CT可激活无功能肾上腺腺瘤组织中的腺苷酸环化酶。CT可使癌组织质膜上的43 kDa蛋白发生ADP核糖基化，而CT和PT分别可使腺瘤组织中的43 kDa和38 kDa蛋白发生ADP核糖基化。对癌组织的免疫印迹分析表明，抗Gs抗体和抗Gi抗体均可检测到40 kDa蛋白。本实验表明，CT可使对腺苷酸环化酶有刺激作用的Gs以及抑制腺苷酸环化酶的Gi发生ADP核糖基化。因此，提示CT可激活人类肾上腺皮质癌组织中Gs和Gi的ADP核糖基化，部分导致腺苷酸环化酶的异常调节，这可能与对ACTH无反应密切相关。
