title: Effect of some drugs on thromboplastin activity in mouse trophoblast cells in vitro and in vivo.
abstract: 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.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015232:Dinoprostone; D015736:Felodipine; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008745:Methylation; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000031:analogs & derivatives / Q000494:pharmacology; D011247:Pregnancy; D011458:Prostaglandins E / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014372:Tubercidin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D011458:Prostaglandins E; C018258:3-deazaadenosine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; C034583:3-deazaaristeromycin; C010192:9-(2-hydroxy-3-nonyl)adenine; D005707:Gallic Acid; D013925:Thromboplastin; D008985:Monensin; D009568:Nitrendipine; D014700:Verapamil; D009543:Nifedipine; D000225:Adenine; D000241:Adenosine; D015232:Dinoprostone; D014372:Tubercidin; D015736:Felodipine; D015056:1-Methyl-3-isobutylxanthine