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

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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 mug PGE(1) per ml. At a concentration of 4 mug/ml, PGE(2) was almost equally effective, but PGF(2alpha) and PGA(2) were much less so. 2.6 muM 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 muM 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.