The Journal of Experimental Medicine, Vol 135, 220-234,
Copyright © 1972 by The Rockefeller University Press
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
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VII. METABOLISM OF ADENOSINE 3',5'-MONOPHOSPHATE IN MICE EXPOSED TO EARLY ENVIRONMENTAL STRESS
Chi-Jen Lee 1 and
René Dubos 1
1 From The Rockefeller University, New York 10021
The metabolism of adenosine 3',5'-monophosphate (cyclic AMP) was studied in specific pathogen-free mice exposed to neonatal infection with mouse enterovirus or to malnutrition during early life. Metabolic activity was determined by measuring the turnover of cyclic AMP-8-14C to respiratory 14CO2, its incorporation into various organs and plasma, and the binding activity of synaptosome for cyclic AMP.
Early malnutrition increased the catabolism of cyclic AMP as measured by expiration in respiratory CO2. The level of cyclic AMP was lower in plasma and its incorporation into various tissues was decreased in infected and malnourished animals. Metabolic products of cyclic AMP were isolated from plasma by ion exchange chromatography. Cyclic AMP-8-14C had completely disappeared 9 hr after injection. Fewer metabolites of cyclic AMP were detected in infected or malnourished groups than in controls and the metabolic reaction from 5'-AMP to adenosine seemed to be slow in these animals. The ability to incorporate cyclic AMP to synaptosome was also impaired in the experimental groups.
The concentrations of brain cyclic AMP were lower in infected or malnourished animals than in controls. Depression of accumulation of cyclic AMP probably resulted from excessive activity of phosphodiesterase, rather than from impairment of adenyl cyclase. Intraperitoneal administration of theophylline brought the activity level of phosphodiesterase to normal in infected or malnourished mice; this fact probably accounted for enhanced accumulation of brain cyclic AMP.
Submitted on September 30, 1971
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