PGE 2 attenuates PGF 2α-induced increases in free intracellular calcium in ovine large luteal cells

Abstract

When ovine large luteal cells are placed in culture and exposed to PGF 2α, 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 PGF 2α. Since administration of exogenous PGE 2 can prevent spontaneous and PGF 2α-induced luteolysis in vivo, and the cytotoxic effects of PGF 2α on large luteal cells in vitro, the objective of this study was to determine if one mechanism by which PGE 2 acts is to attenuate increases in free intracellular calcium induced by PGF 2α. At concentrations of 10 nM or greater, PGF 2α caused a significant and sustained increase in free intracellular calcium in large luteal cells. Similarly, PGE 2 also induced increases in free intracellular calcium but required doses 20-fold greater than PGF 2α. When PGE 2 (1, 10 or 100 nM) was incubated with PGF 2α (100 nM) increases in free intracellular calcium induced by PGF 2α 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 PGF 2α was the result of fewer cells responding to PGF 2α. In addition, the concentrations of free intracellular calcium attained in the cells that did respond was reduced 25% compared to cells treated with PGF 2α alone. Thus, part of the luteal protective actions of PGE 2 appears to involve an inhibition of the early (5 min) increase in free intracellular calcium induced by PGF 2α.