Prostaglandin E1 Effects on Adenosine 3′:5′-Cyclic Monophosphate Concentration and Phosphodiesterase Activity in Fibroblasts

AUTOR(ES)

Maganiello, Vincent

RESUMO

Incubation of L-929 and L-2071 fibroblasts with prostaglandin E1 (PGE1) caused a rapid increase in the cyclic AMP content of these cells. A maximal effect was produced with 0.2 μg PGE1 per ml. At a concentration of 4 μg/ml, PGE2 was almost equally effective, but PGF2α and PGA2 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 PGE1 in a concentration sufficient to increase maximally the cyclic AMP content of cells not previously exposed to this compound. A second addition of PGE1 after 5 or 24 hr did not produce another increase in the concentration of cyclic AMP. After incubation with PGE1 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 PGE1 that develops after incubation for several hours with this compound.

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