monensin and 3-deazaadenosine

Mouse trophoblast cells are constitutive producers of the thromboplastin apoprotein in vitro. The effects on thromboplastin activity of the three transmethylation inhibitors 3-deazaadenosine (DZA), 3-deazaaristeromycin (DZAri) and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), the four calcium antagonists TMB-8, verapamil, nifedipine and felodipine, the prostaglandin E2 (PGE2), the phosphodiesterase inhibitor 1-methyl 3-isobutylxanthine (MIX) and monensin have been studied. No cytotoxic effects were detected when trypan blue exclusion, release of lactic dehydrogenase, incorporation of 14C-leucine into protein and cell morphology were monitored. TMB-8, felodipine, nifedipine and verapamil all abolished the increase in thromboplastin when added after 68 hr or 90-96 hr in culture. EHNA and DZAri had the same effect (but were only added at 90-96 hr). DZA had a similar effect when added at 68 hr and an even more marked inhibitory effect when added at 90-96 hr. Monensin prevented the increase in thromboplastin activity at 68 hr as well as at 90-96 hr. The combination of DZA and 1-homocysteine thiolactone (Hcy) further increased the inhibition, indicating that in these cases synthesis as well as degradation of thromboplastin were altered. The combination of DZA/Hcy and one of the four calcium antagonists gave no additional inhibitory effect. PGE2 had a biphasic dose-dependent effect. The increased thromboplastin activity at low concentrations of PGE2 (10 ng/ml) was inhibited by addition of one of the compounds verapamil, felodipine, nifedipine or DZA/Hcy. PGE2 at higher levels (10 micrograms/ml) significantly inhibited thromboplastin synthesis. Combination of PGE2 (10 micrograms/ml) and one of the calcium antagonists, DZA/Hcy or MIX gave no significant additive inhibitory effect.

Topics: 1-Methyl-3-isobutylxanthine; Adenine; Adenosine; Animals; Calcium Channel Blockers; Dinoprostone; Felodipine; Female; Gallic Acid; Methylation; Mice; Monensin; Nifedipine; Nitrendipine; Pregnancy; Prostaglandins E; Thromboplastin; Trophoblasts; Tubercidin; Verapamil