PGE2 attenuates PGF2 alpha-induced increases in free intracellular calcium in ovine large luteal cells

When ovine large luteal cells are placed in culture and exposed to PGF2 alpha, there is a rapid and sustained increase in the concentration of free intracellular calcium which is believed to play a major role in the luteolytic and cytotoxic effects of PGF2 alpha. Since administration of exogenous PGE2 can prevent spontaneous and PGF2 alpha-induced luteolysis in vivo, and the cytotoxic effects of PGF2 alpha on large luteal cells in vitro, the objective of this study was to determine if one mechanism by which PGE2 acts is to attenuate increases in free intracellular calcium induced by PGF2 alpha. At concentrations of 10 nM or greater, PGF2 alpha caused a significant and sustained increase in free intracellular calcium in large luteal cells. Similarly, PGE2 also induced increases in free intracellular calcium but required doses 20-fold greater than PGF2 alpha. When PGE2 (1, 10 or 100 nM) was incubated with PGF2 alpha (100 nM) increases in free intracellular calcium induced by PGF2 alpha were attenuated (P < 0.05) when measured 5 min, but not at 30 min, after initiation of treatment. The observed decrease in the concentration of free intracellular calcium at 5 min in response to PGF2 alpha was the result of fewer cells responding to PGF2 alpha. In addition, the concentrations of free intracellular calcium attained in the cells that did respond was reduced 25% compared to cells treated with PGF2 alpha alone. Thus, part of the luteal protective actions of PGE2 appears to involve an inhibition of the early (5 min) increase in free intracellular calcium induced by PGF2 alpha.