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Prostaglandin E(1) Effects on Adenosine 3′:5′-Cyclic Monophosphate Concentration and Phosphodiesterase Activity in Fibroblasts

By Vincent Maganiello and Martha Vaughan

Abstract

Incubation of L-929 and L-2071 fibroblasts with prostaglandin E(1) (PGE(1)) caused a rapid increase in the cyclic AMP content of these cells. A maximal effect was produced with 0.2 μg PGE(1) per ml. At a concentration of 4 μg/ml, PGE(2) was almost equally effective, but PGF(2α) and PGA(2) were much less so. 2.6 μM epinephrine, 0.4 mM serotonin, and 0.2% ethanol were without effect. In L-929 cells, cyclic AMP concentrations remained elevated for 2-5 hr, and then declined, although even after a 24-hr incubation the medium contained PGE(1) in a concentration sufficient to increase maximally the cyclic AMP content of cells not previously exposed to this compound. A second addition of PGE(1) after 5 or 24 hr did not produce another increase in the concentration of cyclic AMP. After incubation with PGE(1) for 24 hr, cyclic AMP phosphodiesterase activity, assayed with 0.56 μM substrate, was increased 30-100%; the activity rose further between 24 and 48 hr. It is suggested that the increase in phosphodiesterase activity that appears to be a consequence of prolonged elevation of cyclic AMP concentration may account at least in part for the apparent “refractoriness” to PGE(1) that develops after incubation for several hours with this compound

Topics: Biological Sciences: Biochemistry
Year: 1972
DOI identifier: 10.1073/pnas.69.1.269
OAI identifier: oai:pubmedcentral.nih.gov:427589
Provided by: PubMed Central
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