Kowal J, Srinivasan S
Endocr Res Commun. 1975;2(1):65-86. doi: 10.1080/07435807509053839.
Primary cultures of mouse adrenocortical tumors provide a sensitive system for investigating the effects of the enterotoxin of the V. cholerae (choleragen) on cyclic-AMP metabolism in the intact cell. Like ACTH, the toxin stimulates the synthesis and release of steroids from these cells but its mode of action differs from that of ACTH. The steroidogenic response to ACTH is immediate and of limited duration. The initial rate of steroidogenesis is the highest. In contrast, the steroidogenic response to choleragen is preceded by a 30-240 minute lag period which is inversely related to the concentration of the toxin. Whereas prolongation of the response to a single dose of ACTH requires hormone concentrations above those producing maximal initial steroidogenic activity, persistent steroidogenesis is induced at all levels of the toxin. Steroidogenic responses are detectable with 10 pg/ml of choleragen or less. The respective effects of ACTH and choleragen on cyclic-AMP synthesis and release into the medium parallel those on steroidogenesis. Intracellular cyclic-AMP levels in ACTH-treated cells reach a peak within 20-30 minutes and decline to normal levels within 2-4 hours. In choleragen-treated cells, after the lage period, the levels of intracellular cyclic-AMP remain above control levels indefinitely. The effects of ACTH and choleragen on cyclic-AMP biosynthesis are additive at all levels of the two compounds. The effects of choleragen are blocked by prior treatment of the toxin with a five-fold molar excess of ganglioside GM1, a presumed constituent of the toxin-binding site.
小鼠肾上腺皮质肿瘤的原代培养物为研究霍乱弧菌肠毒素（霍乱原）对完整细胞中环磷酸腺苷（cAMP）代谢的影响提供了一个敏感的系统。与促肾上腺皮质激素（ACTH）一样，该毒素能刺激这些细胞中类固醇的合成和释放，但其作用方式与ACTH不同。对ACTH的类固醇生成反应是即时的，且持续时间有限。类固醇生成的初始速率最高。相比之下，对霍乱原的类固醇生成反应之前有30 - 240分钟的延迟期，该延迟期与毒素浓度呈负相关。虽然对单剂量ACTH反应的延长需要高于产生最大初始类固醇生成活性的激素浓度，但在所有毒素水平下均可诱导持续的类固醇生成。10 pg/ml或更低浓度的霍乱原就能检测到类固醇生成反应。ACTH和霍乱原对cAMP合成及释放到培养基中的各自影响与它们对类固醇生成的影响相似。用ACTH处理的细胞内cAMP水平在20 - 30分钟内达到峰值，并在2 - 4小时内降至正常水平。在经霍乱原处理的细胞中，延迟期过后，细胞内cAMP水平会无限期地保持在对照水平之上。在两种化合物的所有水平下，ACTH和霍乱原对cAMP生物合成的影响都是相加的。用五倍摩尔过量的神经节苷脂GM1（一种推测的毒素结合位点成分）预先处理毒素，可阻断霍乱原的作用。
