A NEW PRINCIPLE FOR RESISTANCE TO CHOLERA - DESENSITIZATION TO CYCLIC AMP-MEDIATED DIARRHEA INDUCED BY CHOLERA-TOXIN IN THE MOUSE INTESTINE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 7  (4) , 247-257
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 8-16 days. The desensitization to CT was totally reversed by a 4 h treatment with cycloheximide, an inhibitor of protein synthesis. Neither the secretory response to dibutyryl-cAMP 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. Intestinal resistance to CT is apparently mainly a function of AC-desensitization mediated by an inducable protein.