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• W2124254865 startingPage "794" @default.
• W2124254865 abstract "ABSTRACT Cholera toxin (CT) increases intestinal secretion of water and electrolytes and modulates the mucosal immune response by stimulating cellular synthesis of arachidonic acid (AA) metabolites (e.g., prostaglandin E 2 ), as well as the intracellular second messenger cyclic AMP (cAMP). While much is known about the mechanism of CT stimulation of adenylate cyclase, the toxin’s activation of phospholipase A 2 , which results in increased hydrolysis of AA from membrane phospholipids, is not well understood. To determine whether CT activation of AA metabolism requires CT’s known enzymatic activity (i.e., ADP-ribosylation of G Sα ), we used native CT and a mutant CT protein (CT-2*) lacking ADP-ribose transferase activity in combination with S49 wild-type (WT) and S49 cyc − murine Theta (Th)1.2-positive lymphoma cells deficient in G Sα . The experimental results showed that native CT stimulated the release of [ 3 H[AA from S49 cyc − cells at a level similar to that for S49 WT cells, indicating that G Sα is not essential for this process. Further, levels of cAMP in the CT-treated cyc − cells remained the same as those in the untreated control cells. The ADP-ribosyltransferase-deficient CT-2* protein, which was incapable of increasing synthesis of cAMP, displayed about the same capacity as CT to evoke the release of [ 3 H]AA metabolites from both S49 WT and cyc − cells. We concluded that stimulation of arachidonate metabolism in S49 murine lymphoma cells by native CT does not require enzymatically functional CT, capable of catalyzing the ADP-ribosylation reaction. These results demonstrated for the first time that stimulation of adenylate cyclase by CT and stimulation of AA metabolism by CT are not necessarily coregulated. In addition, the B subunits purified from native CT and CT-2* both simulated the release of [ 3 H]AA from S49 cyc − cells and murine monocyte/macrophage cells (RAW 264.7), suggesting a receptor-mediated cell activation process of potential importance in enhancing immune responses to vaccine components." @default.
• W2124254865 created "2016-06-24" @default.
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• W2124254865 date "1999-02-01" @default.
• W2124254865 modified "2023-09-27" @default.
• W2124254865 title "Cholera Toxin B Subunit Activates Arachidonic Acid Metabolism" @default.
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• W2124254865 doi "https://doi.org/10.1128/iai.67.2.794-799.1999" @default.
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