ISSN:
1573-4919
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
Summary In HeLa S3 cultures, exogenous cAMP and its dibutyryl derivative (DBcAMP) produced divergent effects with respect to glycogen levels as well as to incorporation of labeled precursors into nucleic acids, concentration of nucleotide triphosphates, and the extent of cell proliferation inhibition. The actions of exogenous cAMP were unspecific, as they could be imitated by various adenine nucleotides. Evidence is presented which shows that all effects seen with exogenous cAMP were brought about by adenosine set free continuously by the action of extracellular enzymes. Adenosine, when provided continuously by infusion or enzymically from exogenous adenine nucleotides, caused a depletion of pyrimidine nucleotides and a subsequent inhibition of net nucleic acid formation and of cell proliferation. The increased incorporation rates of (3H)uridine and (3H)thymidine into nucleic acids seen under these conditions were also consequences of the altered precursor pool sizes. Continuous provision of adenosine leading to effective cytostasis could also be achieved in tumor-bearing animals when high doses of adenine nucleotides like cAMP or NAD were injected. DBcAMP was able to imitate intracellular cAMP only after conversion to N6-monobutyryl cAMP which accumulated inside the cells and which had a high affinity to a muscle protein kinase. N6-MBcAMP also inhibited HeLa cAMP phosphodiesterases (low and high Km) competitively and to a similar degree as DBcAMP and theophylline. This inhibition, however, does not seem to contribute significantly to the effects of DBcAMP in HeLa cultures. The actions opposite to DBcAMP of exogenous cAMP disappeared when its extracellular degradation was prevented by theophylline or by heat-inactivation of the serum used in the culture medium. Its effects under these conditions, however, were still less pronounced than the alterations caused by DBcAMP.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01659332
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