Premium
Uterus‐relaxing effect of β 2 ‐agonists in combination with phosphodiesterase inhibitors: Studies on pregnant rat in vivo and on pregnant human myometrium in vitro
Author(s) -
Verli Judit,
Klukovits Anna,
Kormányos Zsolt,
HajagosTóth Judit,
Ducza Eszter,
Seres Adrienn B.,
Falkay George,
Gáspár Róbert
Publication year - 2013
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/j.1447-0756.2012.01929.x
Subject(s) - rolipram , terbutaline , myometrium , phosphodiesterase , oxytocin , uterus , in vivo , medicine , uterine contraction , endocrinology , tocolytic , ex vivo , pharmacology , fetus , preterm labor , chemistry , pregnancy , enzyme , biology , biochemistry , genetics , microbiology and biotechnology , asthma
Aims: Our aims were to examine the effects of a simultaneous stimulation of β 2 ‐adrenergic receptors and inhibition of uterine phosphodiesterases (PDE), in the pregnant rat uterus in vivo and on human uterine tissue in vitro. We also set out to measure cAMP levels and detect the expressions of the isoenzymes PDE4B and PDE4D in human uterine tissue samples. Material and Methods: Preterm birth was induced in Sprague‐Dawley rats with bacterial lipopolysaccharide. The uterine effects of terbutaline alone or in combination with rolipram were tested in vivo . Human myometrial strips from cesarean sections at full‐term pregnancy and at preterm labor were stimulated with oxytocin, and the inhibitory effects of theophylline, rolipram and terbutaline were studied. The myometrial accumulation of cAMP in the presence of rolipram and terbutaline was determined by enzyme immunoassay. The expressions of PDE4B and PDE4D proteins were detected by Western blotting. Results: The selective PDE4 inhibitor rolipram was more effective than the non‐selective PDE inhibitor theophylline in inhibiting the oxytocin‐induced contractions in the human uterus. The uterus‐relaxing effects of low doses of terbutaline were markedly potentiated by rolipram, both in rats and in human tissues. The changes in uterine cAMP levels correlated with these results. At preterm labor, PDE4B was the predominant form of PDE4 expressed; at full term, PDE4D was expressed more strongly. Conclusions: A combination of selective PDE4 inhibitors and β 2 ‐agonists should be considered for the treatment of preterm contractions.