The effects of epinephrine and prostaglandin E-1 on cyclic adenosine 3':5'-monophosphate levels in WI-38 fibroblasts.

1. Intact WI-38 human diploid lung fibroblasts were shown to respond to epinephrine (3 X lop7 M) and prostaglandin El (PGE1) (0.57 X lop7 M) with increased cyclic adenosine 3’: 5’-monophosphate (cyclic AMP) levels. Corticotropin (1.25 units per ml), insulin (0.02 to 200 milliunits per ml), and glucagon (5 X lo-’ M) were ineffective. Although the response to PGE, was not clearly maximal at concentrations up to 2.8 X 10e5 M, the response to 5.7 X 10e6 M PGEl was greater than the maximal response to epinephrine (10 X lop6 M) under all conditions studied. 2. Theophylline (2 mM) potentiated the action of PGEl on cyclic AMP levels by at least 2-fold in all experiments, but W&LO less effective with epinephrine; in several experiments theophylline did not potentiate the effects of the catecholamine. 3. Propranolol (0.1 mM) completely inhibited the effect of epinephrine but only slightly diminished that of PGE1. 4. Cells grown to high population density responded poorly or not at all to epinephrine while cells at low population densities responded very well. A converse relationship was observed between PGEl action and population density, although it was not as dramatic. The effect of population density on the epinephrine stimulation did not appear to be due to a difference in sensitivity of the populations to epinephrine. 5. Cyclic AMP appeared in the incubation medium of WI38 cells treated with epinephrine or PGE1. This appearance reached maximal levels more slowly than did intracellular cyclic AMP but represented a considerable amount of cyclic nucleotide.