Uterus-relaxing effect of β2-agonists in combination with phosphodiesterase inhibitors: Studies on pregnant rat in vivo and on pregnant human myometrium in vitro

Judit Verli, Anna Klukovits, Zsolt Kormányos, Judit Hajagos-Tóth, Eszter Ducza, Adrienn B. Seres, G. Falkay, R. Gáspár

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish
Pages (from-to)31-39
Number of pages9
JournalThe journal of obstetrics and gynaecology research
Volume39
Issue number1
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Rolipram
Phosphodiesterase Inhibitors
Myometrium
Terbutaline
Uterus
Phosphodiesterase 4 Inhibitors
Premature Obstetric Labor
Oxytocin
Theophylline
Premature Birth
Phosphoric Diester Hydrolases
Immunoenzyme Techniques
Cesarean Section
Adrenergic Receptors
Isoenzymes
Sprague Dawley Rats
Lipopolysaccharides
Western Blotting
In Vitro Techniques
Pregnancy

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 journalArticle

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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.",
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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.

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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.

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