Abstract
Aims: Our aims were to examine the effects of a simultaneous stimulation of β2-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 β2-agonists should be considered for the treatment of preterm contractions.
| Original language | English |
|---|---|
| Pages (from-to) | 31-39 |
| Number of pages | 9 |
| Journal | The journal of obstetrics and gynaecology research |
| Volume | 39 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2013 |
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Keywords
- β-mimetics
- Phosphodiesterase
- Preterm labor
- Rolipram
- Terbutaline
ASJC Scopus subject areas
- Obstetrics and Gynaecology
Cite this
Uterus-relaxing effect of β2-agonists in combination with phosphodiesterase inhibitors : Studies on pregnant rat in vivo and on pregnant human myometrium in vitro. / Verli, Judit; Klukovits, Anna; Kormányos, Zsolt; Hajagos-Tóth, Judit; Ducza, Eszter; Seres, Adrienn B.; Falkay, G.; Gáspár, R.
In: The journal of obstetrics and gynaecology research, Vol. 39, No. 1, 01.2013, p. 31-39.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Uterus-relaxing effect of β2-agonists in combination with phosphodiesterase inhibitors
T2 - Studies on pregnant rat in vivo and on pregnant human myometrium in vitro
AU - Verli, Judit
AU - Klukovits, Anna
AU - Kormányos, Zsolt
AU - Hajagos-Tóth, Judit
AU - Ducza, Eszter
AU - Seres, Adrienn B.
AU - Falkay, G.
AU - Gáspár, R.
PY - 2013/1
Y1 - 2013/1
N2 - Aims: Our aims were to examine the effects of a simultaneous stimulation of β2-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 β2-agonists should be considered for the treatment of preterm contractions.
AB - Aims: Our aims were to examine the effects of a simultaneous stimulation of β2-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 β2-agonists should be considered for the treatment of preterm contractions.
KW - β-mimetics
KW - Phosphodiesterase
KW - Preterm labor
KW - Rolipram
KW - Terbutaline
UR - http://www.scopus.com/inward/record.url?scp=84875747213&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875747213&partnerID=8YFLogxK
U2 - 10.1111/j.1447-0756.2012.01929.x
DO - 10.1111/j.1447-0756.2012.01929.x
M3 - Article
C2 - 22765375
AN - SCOPUS:84875747213
VL - 39
SP - 31
EP - 39
JO - Journal of Obstetrics and Gynaecology Research
JF - Journal of Obstetrics and Gynaecology Research
SN - 1341-8076
IS - 1
ER -