title: A new principle for resistance to cholera: desensitization to cyclic AMP-mediated diarrhea induced by cholera toxin in the mouse intestine.
abstract: The mechanisms behind the intestinal resistance to cholera toxin was studied in a mouse model. Repeated peroral treatments with cholera toxin (CT) led to a long-lasting inhibition of the toxin-induced activation of intestinal adenylate cyclase (AC). A corresponding inhibition of the intestinal fluid secretion induced not only by CT but also by prostaglandin E1 was observed. This unspecific desensitization was followed by a CT-specific inhibition of secretion and AC after 8 to 16 days. The desensitization to CT was totally reversed by a 4 hour-treatment with cycloheximide, an inhibitor of protein synthesis. Neither the secretory response to dibutyryl-cyclic AMP nor the activity of soluble phosphodiesterase differed between the CT-treated mice and the control group. Nor was the average turn-over rate of intestinal cells changed as judged from the mucosal incorporation of [3H]-thymidine. It is postulated that intestinal resistance to CT is mainly a function of AC-desensitization mediated by an inducible protein.
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002771:Cholera / Q000276:immunology; D002772:Cholera Toxin / Q000009:adverse effects / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced; D004351:Drug Resistance; D007109:Immunity; D007413:Intestinal Mucosa / Q000201:enzymology*; D007421:Intestine, Small / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011458:Prostaglandins E / Q000494:pharmacology
chemical_list: D011458:Prostaglandins E; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D000527:Alprostadil