Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium.
The recently developed xanthine derivate, enprofylline, was studied in an in vitro system with human pregnant myometrium, in particular its effect on spontaneous myometrial contraction, cyclic adenosine monophosphate content, cyclic adenosine monophosphate protein kinase, and cyclic adenosine monophosphate-and cyclic guanosine monophosphate-dependent phosphodiesterase activity. Enprofylline was shown to be a rather potent smooth muscle relaxant [inhibitory concentration that decreases response by 50% (IC50) = 3 X 10(-5) mol/L] and an almost equally potent cyclic adenosine monophosphate-dependent phosphodiesterase inhibitor (IC50 = 10(-4) mol/L), whereas it was a less potent cyclic guanosine monophosphate-dependent phosphodiesterase inhibitor. Enzyme kinetic studies revealed that enprofylline is a competitive cyclic adenosine monophosphate phosphodiesterase inhibitor. Enprofylline increased the cyclic adenosine monophosphate content in a dose-dependent way with subsequent increased activity of cyclic adenosine monophosphate-dependent protein kinase. It is suggested that enprofylline relaxes myometrial smooth muscles and that this is at least partly the result of interference with the cyclic adenosine monophosphate system.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D009130:Muscle, Smooth / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000201:enzymology; D011247:Pregnancy / Q000187:drug effects* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology*
D014970:Xanthines; C034347:enprofylline; D000242:Cyclic AMP; D011494:Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases