Decidual adenylate cyclase and prostaglandin production in vitro.
Human decidua contains an active adenylate cyclase, and a number of studies indicate that adenylate cyclase is functionally linked to increased in vitro prostaglandin synthesis. Increased decidual prostaglandin synthesis is associated with parturition, and therefore activation of adenylate cyclase may be involved in the control of human parturition. In this study, third trimester human decidual cells were preincubated for no more than 24 h prior to stimulation with a number of reagents which increase cellular cyclic AMP levels. Forskolin rapidly increased intracellular and extracellular cyclic AMP levels, but there was no increase in prostaglandin E2 biosynthesis during incubations ranging from 5 min up to 24 h. Dibutyryl cyclic AMP or 8-bromo-cyclic AMP were also without effect on PGE2 production, which suggests that the adenylate cyclase was not linked to the mechanisms regulating prostaglandin production. Cholera toxin increased basal cyclic AMP and PGE2 synthesis, and was without effect on IL-1 beta-stimulated PGE2 levels. PGE2 synthesis was increased by 24 h culture with IL-1 beta in all the cell preparations, indicating that the cells were biologically active, and that the lack of effect of changes in cyclic AMP synthesis on PGE2 levels could not be attributed to a defect in the prostaglandin synthetic pathway. Our findings did not agree with earlier work which showed that changes in cyclic AMP were correlated with changes in PGE2 production by human decidual cells. It is clear that in the previous studies the decidual cells were preincubated for 4-7 days prior to stimulation, in contrast with 24 h in our investigation.(ABSTRACT TRUNCATED AT 250 WORDS)
Cole
O F
OF
R.P.M.S. Institute of Obstetrics & Gynaecology, Hammersmith Hospital, London, UK.
Elder
M G
MG
Sullivan
M H
MH
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D003656:Decidua / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D011247:Pregnancy
D007375:Interleukin-1; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone