Peterson J W, Lu Y, Duncan S, Cantu J, Chopra A K
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555-1019.
J Med Microbiol. 1994 Jul;41(1):3-9. doi: 10.1099/00222615-41-1-3.
Cholera toxin (CT) and prostaglandin E2 (PGE2) increased the synthesis of 3',5'-cyclic adenosine monophosphate (cAMP) in rabbit intestinal mucosa, which appeared to be responsible for inducing the release of 5-hydroxytryptamine (5-HT) from enterochromaffin cells into the intestinal lumen. With isolated intestinal cells, CT induced the synthesis of PGE2 more efficiently from epithelial cells than from lamina propria cells; however, the basal amount of this eicosanoid produced by lamina propria cells was approximately six-fold more than that formed by the epithelial cells. The CT-induced stimulation of arachidonate metabolism appeared to be generalised in nature, as PGF2 alpha and leukotrienes were synthesised in addition to PGE2. Injection of dibutyryl cAMP into the intestinal lumen in vivo markedly reduced both basal levels of PGE2, as well as CT-induced levels of PGE2, released into the luminal fluid. Similarly, when biopsy samples of tissue from rabbit intestinal loops, challenged in vivo with dibutyryl cAMP, were washed and incubated in vitro, the amount of PGE2 synthesis remained below basal levels. In contrast, when biopsy samples of normal small intestinal tissue were exposed in vitro to dibutyryl cAMP, PGE2 synthesis increased. Thus, cAMP appeared to down-regulate the levels of intestinal eicosanoids in vivo, despite its innate capacity to evoke PGE2 synthesis from mucosal tissue in vitro. Thus, the data indicate that CT-induced mediators exhibit interactive effects that alter their cellular concentrations, that in turn could affect the biological responses.
霍乱毒素（CT）和前列腺素E2（PGE2）可增加兔肠黏膜中3',5'-环磷酸腺苷（cAMP）的合成，这似乎是导致肠嗜铬细胞将5-羟色胺（5-HT）释放到肠腔中的原因。对于分离的肠细胞，CT从上皮细胞诱导PGE2合成的效率高于从固有层细胞；然而，固有层细胞产生的这种类花生酸的基础量比上皮细胞形成的量大约多六倍。CT诱导的花生四烯酸代谢刺激似乎具有普遍性，因为除了PGE2之外，还合成了前列腺素F2α和白三烯。在体内向肠腔注射二丁酰cAMP可显著降低释放到肠腔液中的PGE2基础水平以及CT诱导的PGE2水平。同样，当用二丁酰cAMP在体内刺激的兔肠袢组织活检样本被冲洗并在体外培养时，PGE2合成量仍低于基础水平。相反，当正常小肠组织的活检样本在体外暴露于二丁酰cAMP时，PGE2合成增加。因此，尽管cAMP在体外具有从黏膜组织诱发PGE2合成的内在能力，但它在体内似乎下调了肠类花生酸的水平。因此，数据表明CT诱导的介质表现出相互作用的效应，改变了它们的细胞浓度，进而可能影响生物学反应。
