PROSTAGLANDIN PRODUCTION BY GUINEA-PIG ENDOMETRIAL CELLS - EFFECTS OFCAFFEINE AND OTHER MODULATORS OF INTRACELLULAR CALCIUM

The glandular epithelial cells were found to be the main source of PGF (2 alpha) (the uterine luteolytic hormone) in guinea-pig endometrium. There was a selective increase in PGF(2 alpha) production by these cel ls in culture at the time of the cycle (i.e. day 15) at which there is increased PGF(2 alpha) release from the guinea-pig uterus in vivo. TM B-8 (an intracellular calcium antagonist), W-7, trifluoperazine (both calmodulin antagonists), thapsigargin (an inhibitor of intracellular c alcium uptake) and berberine (an inhibitor of calcium release) reduced the output of PGF(2 alpha) from day 7 glandular epithelial cells indi cating that intracellular calcium is necessary for PGF(2 alpha) produc tion by these cells. In contrast to its stimulatory effect on PGF(2 al pha) output from the guinea-pig uterus superfused in vitro and guinea- pig endometrium in culture, caffeine inhibited the output of PGF(2 alp ha) from guinea-pig glandular epithelial cells in culture. Its effect was not fully shared by theophylline, nor mimicked by forskolin showin g that cyclic AMP is not involved. The inhibitory actions of caffeine and those of the compounds which interfere with the action of intracel lular calcium were not additive, suggesting that caffeine modulates th e action of intracellular calcium in some way. Caffeine reduced the in tracellular free calcium concentration in endometrial cells, but it wa s not particularly effective in this respect on day 7 glandular epithe lial cells. Caffeine may therefore modulate the action of intracellula r calcium in some other way.