Inhibition of cholera toxin-stimulated intestinal epithelial cell adenylate cyclase by adenosine analogs.
The ability of various adenosine analogs to inhibit cholera toxin activation of the intestinal epithelial cell adenylate cyclase-cyclic AMP system was investigated. After incubation of cells with cholera toxin for 6 hr, large increases in cellular cyclic AMP content were observed. Addition of 2', 5'-dideoxyadenosine during the last 30 min of this 6-hr incubation resulted in 70% reduction in elevated cyclic AMP content. Other analogs were not effective inhibitors. 2', 5'-Dideoxyadenosine was also a potent inhibitor of cholera toxin-activated intestinal cell adenylate cyclase activity with half-maximal inhibition occuring at 16 muM. NaF-stimulated cyclase was less susceptible to inhibition. The data suggest that inhibition by 2', 5'-dideoxyadenosine is due at least in part to direct inhibition of the cholera toxin-activated intestinal adenylate cyclase activity.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000992:Antitoxins / Q000494:pharmacology*; D002478:Cells, Cultured; D002771:Cholera / Q000188:drug therapy; D004789:Enzyme Activation / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000201:enzymology; D014118:Toxins, Biological / Q000494:pharmacology*
D000992:Antitoxins; D014118:Toxins, Biological; D000262:Adenylyl Cyclases; D000241:Adenosine; D005459:Fluorides