Inhibition of heat-labile cholera and Escherichia coli enterotoxins by brefeldin A.
Cholera enterotoxin and the related heat-labile enterotoxins of Escherichia coli enter their target cells through noncoated vesicles, but how the toxins are processed intracellularly and how they get to their targeted enzyme, adenylate cyclase, remain to be defined. Brefeldin A, an inhibitor of the trans-Golgi network, is shown herein to transiently block the morphologic and enzymatic effects of the toxin at a step distal to the initial binding process but prior to activation of adenylate cyclase by the toxin. It is likely, therefore, that these toxins are processed by the Golgi apparatus before trafficking to the membrane adenylate cyclase.
Donta
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Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Beristain
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Tomicic
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D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020126:Brefeldin A; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D003517:Cyclopentanes / Q000494:pharmacology*; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D003517:Cyclopentanes; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D020126:Brefeldin A; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; D000242:Cyclic AMP