Differential Effects of Prostaglandin F2α and of Prostaglandins E1 and E2 on Cyclic 3′, 5′-Monophosphate Production and Intracellular Calcium Mobilization in Avian Uterine Smooth Muscle Cells1

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Abstract
The effects of prostaglandins (PGs) E1 (PGE1), E2 (PGE2) and F2.alpha. (PGF2.alpha.) on cyclic 3'',5''-adenosine monophosphate (cAMP) production and intracellular Ca mobilization were examined in smooth muscle cells of chicken uterus grown in primary culture. At subnanomolar concentrations, both PGE1 and PGE2 significantly suppressed cAMP levels. However, at higher concentrations (0.1-100 .mu.M), both agonists caused a dose-related increase in cAMP production. PGF2.alpha., on the other hand, had no effect on cAMP production. Forskolin (1-100 .mu.M), which also stimulated cAMP production in a dose-dependent fashion, potentiated the effects of both PGE1 and PGE2. In digitonin-permeabilized uterine cells preloaded with 45Ca2+, the addition of PGF2.alpha. caused a biphasic 45Ca2+ efflux. There was a small but significant 45Ca2+ release (10.0 .+-. 1.5%) within 30s (rapid phase), followed by a larger one (32.0 .+-. 2.0%) within 5 min (slow phase). PGE2, at doses above 1 nM (which significantly increased cAMP accumulation), promoted 45Ca2+ sequestration. This action of PGE2 was observed as early as 1 min and was complete by 5 min. In addition, 0.001 nM PGE2 (a dose that was ineffective on 45Ca2+ mobilization) enhanced PGE2.alpha.-induced 45Ca2+ mobilization from 22.5 .+-. 5% to 57.0 .+-. 3.5%. These results show that PGs of the E series have distinctly different effects on cAMP production and intracellular Ca mobilization. PGR2.alpha. action may be linked directly to intracellular Ca mobilization, whereas the effects of PGE may be exerted at multiple sites depending on its local concentration. At low concentrations, its action may be mediated by the suppression of cAMP levels. Finally, PGE may also be important as a potentiator of PGF2.alpha.