Wiepz G J, Wiltbank M C, Kater S B, Niswender G D, Sawyer H R
Department of Physiology, Colorado State University, Fort Collins 80523.
Prostaglandins. 1993 Feb;45(2):167-76. doi: 10.1016/0090-6980(93)90032-3.
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.
当将绵羊大黄体细胞置于培养环境中并暴露于前列腺素F2α(PGF2α)时,细胞内游离钙浓度会迅速且持续升高,据信这在PGF2α的溶黄体和细胞毒性作用中起主要作用。由于外源性前列腺素E2(PGE2)的给药可在体内预防自发性和PGF2α诱导的黄体溶解,以及PGF2α对体外大黄体细胞的细胞毒性作用,本研究的目的是确定PGE2发挥作用的一种机制是否是减弱PGF2α诱导的细胞内游离钙增加。在浓度为10 nM或更高时,PGF2α会导致大黄体细胞内游离钙显著且持续增加。同样,PGE2也会诱导细胞内游离钙增加,但所需剂量比PGF2α大20倍。当PGE2(1、10或100 nM)与PGF2α(100 nM)共同孵育时,在开始处理5分钟后测量,PGF2α诱导的细胞内游离钙增加会减弱(P < 0.05),但在30分钟时不会。观察到的在5分钟时PGF2α诱导的细胞内游离钙浓度降低是由于对PGF2α有反应的细胞减少。此外,与仅用PGF2α处理的细胞相比,有反应的细胞内达到的游离钙浓度降低了25%。因此,PGE2的部分黄体保护作用似乎涉及抑制PGF2α诱导的细胞内游离钙早期(5分钟)增加。