Prostaglandin E 1  effects on adenosine 3':5'-cyclic monophosphate concentration and phosphodiesterase activity in fibroblasts (mouse L cells-tissue culture-enzyme kinetics-prostaglandin homologues).
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.
D000818:Animals; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D003470:Culture Media; D000242:Cyclic AMP / Q000032:analysis*; D006152:Cyclic GMP / Q000494:pharmacology; D005347:Fibroblasts / Q000032:analysis* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D007739:L Cells; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013806:Theophylline / Q000494:pharmacology; D013997:Time Factors
D003470:Culture Media; D011453:Prostaglandins; D013806:Theophylline; D000242:Cyclic AMP; D010744:Phosphoric Monoester Hydrolases; D006152:Cyclic GMP