[Effects of calcium antagonists on prostaglandin E2 production in cultured human amnion cells].
The purpose of this study was to determine the effects of calcium antagonists on the production of prostaglandin E2 (PGE2) in human amnion cells. Primary monolayer cultures of human amnion cells were stimulated by interleukin-1 beta (IL-1 beta), and PGE2 in the culture media was measured. Dihydropyridine calcium antagonists nifedipine, nicardipine and nilvadipine inhibited PGE2 production in a dose-dependent manner with maximal inhibition of 60, 80 and 80%, respectively observed at 100 microM. However, nondihydropyridine calcium antagonists verapamil and diltiazem did not inhibit PGE2 production. On the other hand, EGTA reduced PGE2 production only 32%. In addition, nifedipine, nicardipine and nilvadipine inhibited a cell-free preparation of phospholipase A2 (PLA2) activity in a dose-dependent manner, but verapamil and diltiazem failed to reduce PLA2 activity. In conclusion, the evidence suggests that dihydropyridines inhibit PGE2 production in amnion cells by directly inhibiting PLA2 rather than its actions on calcium channels.
Sanada
H
H
Department of Obstetrics and Gynecology, Akita University School of Medicine.
D000650:Amnion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D003864:Depression, Chemical; D004110:Diltiazem / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D010741:Phospholipases A / Q000096:biosynthesis; D054467:Phospholipases A2; D011247:Pregnancy; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007375:Interleukin-1; C035100:nilvadipine; D004533:Egtazic Acid; D014700:Verapamil; D009529:Nicardipine; D010741:Phospholipases A; D054467:Phospholipases A2; D004110:Diltiazem; D009543:Nifedipine; D015232:Dinoprostone