Inhibition of uterine contractions by rolipram in vitro.

The human myometrium contains two different forms of phosphodiesterase (PDE). One form is characterized by its lack of substrate specificity and its calcium-calmodulin dependence. The other one is selective for cyclic adenosine monophosphate (cAMP). Rolipram (4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone, ZK 62711) is a specific cAMP-PDE inhibitor. The physiological significance of the two forms of PDE is still unknown, particularly the role of the cAMP-specific form in the control of uterine motility. The latter form largely occurs in myometrium of pregnant women near term and is also present during the third trimester of pregnancy. Using isolated guinea-pig uteri it has been shown that rolipram in the concentration of 9 x 10(-4) mol/l caused the organ to remain insensitive to the stimulatory action of oxytocin. 9 x 10(-6) mol/l rolipram led to immediate relaxation of the uterus when it was added to the organ bath after the maximum concentration was reached following oxytocin stimulation. A new drug like rolipram effecting uterine motility in a not receptor-mediated manner might have advantages in comparison to beta-mimetics for the treatment of premature labor.