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Research Article Free access | 10.1172/JCI107231
Division of Clinical Pharmacology, Department of Medicine, and the Cancer Research Institute, University of California Medical Center, San Francisco, California 94122
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21212
Department of Medicine, New York University School of Medicine, New York 10016
Find articles by Bourne, H. in: JCI | PubMed | Google Scholar
Division of Clinical Pharmacology, Department of Medicine, and the Cancer Research Institute, University of California Medical Center, San Francisco, California 94122
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21212
Department of Medicine, New York University School of Medicine, New York 10016
Find articles by Lehrer, R. in: JCI | PubMed | Google Scholar
Division of Clinical Pharmacology, Department of Medicine, and the Cancer Research Institute, University of California Medical Center, San Francisco, California 94122
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21212
Department of Medicine, New York University School of Medicine, New York 10016
Find articles by Lichtenstein, L. in: JCI | PubMed | Google Scholar
Division of Clinical Pharmacology, Department of Medicine, and the Cancer Research Institute, University of California Medical Center, San Francisco, California 94122
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21212
Department of Medicine, New York University School of Medicine, New York 10016
Find articles by Weissmann, G. in: JCI | PubMed | Google Scholar
Division of Clinical Pharmacology, Department of Medicine, and the Cancer Research Institute, University of California Medical Center, San Francisco, California 94122
Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21212
Department of Medicine, New York University School of Medicine, New York 10016
Find articles by Zurier, R. in: JCI | PubMed | Google Scholar
Published March 1, 1973 - More info
Cholera enterotoxin caused a delayed accumulation of adenosine 3′,5′-monophosphate (cyclic AMP) in human leukocytes, associated with an increase in leukocyte adenyl cyclase activity. The action of cholera enterotoxin contrasted with that of other agents which stimulate adenyl cyclase: (a) the effects of the toxin were delayed in onset, while prostaglandin-E1 (PGE1) and isoproterenol acted rapidly; (b) removal of the soluble toxin from the extracellular medium did not abolish its effects on cyclic AMP and inhibition of antigenic histamine release, while removal of PGE1 did prevent its effects; (c) PGE1, but not cholera enterotoxin, stimulated adenyl cyclase activity when added directly to broken cell preparations. Binding of the toxin to leukocytes was rapid and irreversible, and was followed by a gradual increase in cyclic AMP which was not prevented by cycloheximide.
Cholera enterotoxin caused accumulation of cyclic AMP in purified human neutrophils as well as mono-nuclear cells, but did not prevent the extrusion of lysosomal hydrolases from phagocytic cells. The toxin only slightly inhibited the ability of human neutrophils to kill Candida albicans. Thus these results with the toxin cast doubt on previous proposals that cyclic AMP regulates these two functions of neutrophils. The unique action of cholera enterotoxin on cyclic AMP production provides a potentially useful pharmacologic tool, in addition to methylxanthines and dibutyryl cyclic AMP, for testing hypotheses relating cyclic AMP to altered function of leukocytes and, perhaps, of other mammalian cells.