Investigations into the mechanisms controlling prostaglandin production by the guinea-pig placenta: roles of calcium and gonadotrophin-releasing hormone.
The outputs of PGF(2 alpha), PGE(2) and 6-keto-PGF(1 alpha) were higher from the day 29 guinea-pig placenta than from the sub-placenta in culture, with PGF(2 alpha)being the major prostaglandin produced by the placenta. Lack of extracellular calcium reduced the production of all three prostaglandins by the sub-placenta and 6-keto-PGF(1 alpha) production by the placenta, but had no effect on the production of PGF(2 alpha) and PGE(2) by the placenta. EGTA (a calcium chelator) and a low concentration (30 microM) of TMB-8 (an intracellular calcium antagonist) generally inhibited prostaglandin output from the placenta and sub-placenta at various time points during culture, although EGTA had no effect on PGE(2) output from the placenta. Trifluoperazine and W-7 (calmodulin inhibitors) had no inhibitory effect on the outputs of PGF(2 alpha) and PGE(2) from the placenta, nor on the outputs of any prostaglandin from the sub-placenta. However, these two compounds inhibited the output of 6-keto-PGF(1 alpha) from the placenta. Nifedipine and verapamil (calcium channel blocking drugs) generally reduced the outputs of prostaglandins from the placenta and sub-placenta, except verapamil had no inhibitory effect on PGF(2 alpha) output from the sub-placenta. Gonadotrophin-releasing hormone (GnRH) did not stimulate the output of prostaglandins from the placenta, and tended to have a weak inhibitory action on this tissue. On the sub-placenta, GnRH had an initial inhibitory action on the outputs of PGF(2alpha) and 6-keto-PGF(1 alpha), which was then followed by a stimulation of the outputs of PGF(2 alpha) and, to a lesser extent, of PGE(2).
Aitken
H
H
Division of Biomedical and Clinical Laboratory Sciences, The University of Edinburgh, Edinburgh, UK.
Poyser
N L
NL
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006168:Guinea Pigs; D009543:Nifedipine / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis
D002121:Calcium Channel Blockers; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D007987:Gonadotropin-Releasing Hormone; D004533:Egtazic Acid; D009543:Nifedipine; D002118:Calcium