Mode of action of cholera toxin: stabilization of catecholamine-sensitive adenylate cyclase in turkey erythrocytes.
Preincubating turkey erythrocytes with cholera toxin alters their adenylate cyclase (EC 4.6.1.1) system: basal activity, maximal epinephrine-stimulatable activity, and affinity of the enzyme reaction for epinephrine are all increased. Pretreatment of erythrocytes with choleragenoid prevents these changes. Cholera toxin does not alter [(3)H]epinephrine uptake by intact erythrocytes. The increase in epinephrine-stimulatable cyclase activity appears to occur at the expense of fluoride-stimulatable activity, which is decreased by the toxin. In lysates from both toxin-treated and control cells, maximally stimulating amounts of epinephrine and fluoride, when added in combination, have a nearly additive effect on cyclase activity. These observations suggest that the adenylate cyclase system of the turkey erythrocyte may exist in two interconvertible forms, one that is catecholamine-responsive but fluoride-insensitive, and another that is fluoride-sensitive but not coupled to catecholamine receptors. Cholera toxin appears to stabilize the enzyme in its hormone receptor-coupled form.
D000262:Adenylyl Cyclases / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology*; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology; D011956:Receptors, Cell Surface; D013268:Stimulation, Chemical; D014316:Tritium; D014422:Turkeys / Q000097:blood*; D014734:Vibrio cholerae
D004768:Enterotoxins; D011956:Receptors, Cell Surface; D014316:Tritium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005459:Fluorides; D004837:Epinephrine