Ek. Naderali et Nl. Poyser, THE EFFECT OF CAFFEINE ON PROSTAGLANDIN OUTPUT FROM THE GUINEA-PIG UTERUS, British Journal of Pharmacology, 113(1), 1994, pp. 103-110
1 Caffeine increased the outputs of prostaglandin F-2 alpha, (PGF(2 al
pha), PGE(2) and 6-keto-PGF(1 alpha), from the guinea-pig uterus on da
ys 7 and 15 of the oestrous cycle. The effect on PGE(2) output depende
d on the: age of the animals and was absent in younger guinea-pigs (<4
months). Theophylline also stimulated the outputs of PGF, and 6-keto-
PGF(1 alpha), but not the output of PGE(2), from the day 7 guinea-pig
uterus. 2 The stimulatory effects of caffeine on the outputs of PGF(2
alpha), PGE(2) and 6-keto-PGF(1 alpha), from the guinea-pig uterus wer
e not prevented by lack of extracellular calcium, ryanodine or rutheni
um red (both inhibitors of calcium release via the ryanodine receptor)
, although the increase in PGF(2 alpha) output tended to be slower whe
n extracellular calcium was absent. Also, ryanodine flattened and broa
dened the peak of increased PGF(2 alpha), release. 3 The calmodulin an
tagonists, W-7 and trifluoperazine, had no inhibitory effect on the ca
ffeine-stimulated increases in uterine prostaglandin output. In fact,
W-7 (but not trifluoperazine) greatly potentiated the action of caffei
ne on uterine PGF(2 alpha), output, but had little or no potentiating
effect on the action of caffeine on uterine PGE(2) and 6-keto-PGF(1 al
pha) outputs. 4 TMB-8, an intracellular calcium antagonist, inhibited
the increase in PGF(2), output produced by caffeine without preventing
the increases in outputs of PGE(2) and 6-keto-PGF(1 alpha). 5 These s
tudies suggest that caffeine stimulates uterine PGF(2 alpha) synthesis
and release by a mechanism dependent upon intracellular calcium, but
this mechanism is not mediated by activation of any of the three well-
characterized ryanodine receptors or by calmodulin. Furthermore, the i
ncreases in the synthesis and release of PGE(2) and 6-keto-PGF(1 alpha
) in the guinea-pig uterus induced by caffeine appear to involve mecha
nism(s) different from that which stimulates PGF(2 alpha), production.