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The effect of caffeine on prostaglandin output from the guinea‐pig uterus
Author(s) -
Naderali E.K.,
Poyser N.L.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16180.x
Subject(s) - caffeine , endocrinology , medicine , trifluoperazine , calcium , alpha (finance) , ryanodine receptor , prostaglandin , guinea pig , chemistry , biology , calmodulin , construct validity , nursing , patient satisfaction
1 Caffeine increased the outputs of prostaglandin F 2α (PGF 2α ), PGE 2 and 6‐keto‐PGF 1α from the guinea‐pig uterus on days 7 and 15 of the oestrous cycle. The effect on PGE 2 output depended on the age of the animals and was absent in younger guinea‐pigs (<4 months). Theophylline also stimulated the outputs of PGF 2α and 6‐keto‐PGF 1α , but not the output of PGE 2 , from the day 7guinea‐pig uterus. 2 The stimulatory effects of caffeine on the outputs of PGF 2α , PGE 2 and 6‐keto‐PGF 1α from the guinea‐pig uterus were not prevented by lack of extracellular calcium, ryanodine or ruthenium red (both inhibitors of calcium release via the ryanodine receptor), although the increase in PGF 2α output tended to be slower when extracellular calcium was absent. Also, ryanodine flattened and broadened the peak of increased PGF 2α release. 3 The calmodulin antagonists, W‐7 and trifluoperazine, had no inhibitory effect on the caffeine‐stimulated increases in uterine prostaglandin output. In fact, W‐7 (but not trifluoperazine) greatly potentiated the action of caffeine on uterine PGF 2α output, but had little or no potentiating effect on the action of caffeine on uterine PGE 2 and 6‐keto‐PGF 1α outputs. 4 TMB‐8, an intracellular calcium antagonist, inhibited the increase in PGF 2α output produced by caffeine without preventing the increases in outputs of PGE 2 and 6‐keto‐PGF 1α . 5 These studies suggest that caffeine stimulates uterine PGF 2α 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 increases in the synthesis and release of PGE 2 and 6‐keto‐PGF 1α in the guinea‐pig uterus induced by caffeine appear to involve mechanism(s) different from that which stimulates PGF 2α production.