Correlation between selective inhibition of the cyclic nucleotide phosphodiesterases and the contractile activity in human pregnant myometrium near term.
The present study was carried out to determine the ability of various pharmacological agents to selectively inhibit each cytosolic form of phosphodiesterase isolated from the longitudinal layer of human myometria near term. Among the drugs tested, zaprinast specifically inhibits the first form of PDE which hydrolyses both substrates (cAMP and cGMP) and is stimulated by the Ca2+-calmodulin complex. A second form of PDE specific for cAMP hydrolysis and Ca2+-calmodulin insensitive is only present during pregnancy. Rolipram is the most potent and selective inhibitor of this second form. It is also the most efficient compound to inhibit in vitro the spontaneous contractions of near term myometria. The double effect of rolipram suggests an important role of the second form of PDE in the mechanisms of contractility during the pregnancy. In addition rolipram or other derivatives might be of a therapeutic interest in the prevention of prematurity in so far as they are devoid of undesirable maternal and fetal side effects.
Leroy
M J
MJ
INSERM U-166, Maternité Baudelocque, Paris, France.
Cedrin
I
I
Breuiller
M
M
Giovagrandi
Y
Y
Ferre
F
F
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D011247:Pregnancy / Q000502:physiology*; D011760:Pyrrolidinones / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D020889:Rolipram; D014590:Uterine Contraction / Q000187:drug effects*; D014631:Valerates / Q000494:pharmacology
D011760:Pyrrolidinones; D015363:Quinolones; D014631:Valerates; C021294:cilostamide; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D020889:Rolipram; C055998:valeramide