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.

Maganiello, V., & Vaughan, M. (1972). Prostaglandin E 1 Effects on Adenosine 3′:5′-Cyclic Monophosphate Concentration and Phosphodiesterase Activity in Fibroblasts. Proceedings of the National Academy of Sciences, 69(1), 269–273.