Prostaglandin synthesis in rat embryo tissue: the effect of non-steroidal anti-inflammatory drugs in vivo and ex vivo.
Aspirin and salicylate are well-known but poorly understood teratogens in laboratory animals. Because aspirin inhibits PG synthesis, we systematically examined PG synthesis in rat embryo homogenates, the inhibition of PG synthesis in vivo and ex vivo by various non-steroidal anti-inflammatory drugs, and tested the hypothesis that the inhibition of PG synthesis is responsible for aspirin-induced limb defects in rats. We report that embryonic rat homogenates synthesize 6-keto-PGF1alpha, PGE, and PGF in large amounts from endogenous substrate, that aspirin and other non-steroidal anti-inflammatory drugs inhibit PG synthesis in vitro but not necessarily in vivo, and that contrary to our original hypothesis, the inhibition of PG synthesis is likely not responsible for aspirin-induced limb defects in rats.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D011247:Pregnancy; D011458:Prostaglandins E / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000096:biosynthesis*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D011458:Prostaglandins E; D011460:Prostaglandins F; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D001241:Aspirin; D007213:Indomethacin