Prostaglandin production by guinea-pig endometrial cells: effects of caffeine and other modulators of intracellular calcium

The glandular epithelial cells were found to be the main source of PGF2 alpha (the uterine luteolytic hormone) in guinea-pig endometrium. There was a selective increase in PGF2 alpha production by these cells in culture at the time of the cycle (i.e. day 15) at which there is increased PGF2 alpha release from the guinea-pig uterus in vivo. TMB-8 (an intracellular calcium antagonist), W-7, trifluoperazine (both calmodulin antagonists), thapsigargin (an inhibitor of intracellular calcium uptake) and berberine (an inhibitor of calcium release) reduced the output of PGF2 alpha from day 7 glandular epithelial cells indicating that intracellular calcium is necessary for PGF2 alpha production by these cells. In contrast to its stimulatory effect on PGF2 alpha output from the guinea-pig uterus superfused in vitro and guinea-pig endometrium in culture, caffeine inhibited the output of PGF2 alpha from guinea-pig glandular epithelial cells in culture. Its effect was not fully shared by theophylline, nor mimicked by forskolin showing that cyclic AMP is not involved. The inhibitory actions of caffeine and those of the compounds which interfere with the action of intracellular calcium were not additive, suggesting that caffeine modulates the action of intracellular calcium in some way. Caffeine reduced the intracellular free calcium concentration in endometrial cells, but it was not particularly effective in this respect on day 7 glandular epithelial cells. Caffeine may therefore modulate the action of intracellular calcium in some other way.