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Research Article Free access | 10.1172/JCI106564

Cyclic 3′,5′-adenosine monophosphate in the human leukocyte: synthesis, degradation, and effects on neutrophil candidacidal activity

Henry R. Bourne, Robert I. Lehrer, Martin J. Cline, and Kenneth L. Melmon

Division of Clinical Pharmacology, Department of Medicine Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Division of Clinical Pharmacology, Department of Pharmacology, Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Find articles by Bourne, H. in: PubMed | Google Scholar

Division of Clinical Pharmacology, Department of Medicine Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Division of Clinical Pharmacology, Department of Pharmacology, Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Find articles by Lehrer, R. in: PubMed | Google Scholar

Division of Clinical Pharmacology, Department of Medicine Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Division of Clinical Pharmacology, Department of Pharmacology, Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Find articles by Cline, M. in: PubMed | Google Scholar

Division of Clinical Pharmacology, Department of Medicine Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Division of Clinical Pharmacology, Department of Pharmacology, Cardiovascular Research Institute and Cancer Research Institute, University of California Medical Center, San Francisco, California 94122

Find articles by Melmon, K. in: PubMed | Google Scholar

Published April 1, 1971 - More info

Published in Volume 50, Issue 4 on April 1, 1971
J Clin Invest. 1971;50(4):920–929. https://doi.org/10.1172/JCI106564.
© 1971 The American Society for Clinical Investigation
Published April 1, 1971 - Version history
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Abstract

Prostaglandins E1 and E2 (PGE1 and PGE2) stimulate adenyl cyclase activity in broken cell preparations of normal human leukocytes, whereas prostaglandin F1a produces no effect. PGE1 and PGE2 also cause increased accumulation of cyclic 3′,5′-adenosine monophosphate-3H (3H-labeled AMP) in intact leukocytes which have been preincubated with adenine-3H in vitro. Theophylline inhibits leukocyte phosphodiesterase activity and potentiates the stimulatory effect of the prostaglandins on intracellular accumulation of cyclic 3′,5′-AMP-3H.

The ability of human granulocytes in vitro to kill Candida albicans was consistently inhibited by PGE1 and theophylline. This effect was reproduced by dibutyryl cyclic 3′,5′-AMP, a lipid-soluble analogue of the endogenous nucleotide. The inhibition of candidacidal activity could not be accounted for by drug effects on phagocytosis, oxygen consumption, or hexose monophosphate shunt activity. These results are consistent with the hypothesis that increased intracellular concentrations of cyclic 3′,5′-AMP impair the granulocyte's ability to kill C. albicans, but the precise mechanism of inhibition has not yet been defined.

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