Improving the relaxing effect of terbutaline with phosphodiesterase inhibitors

Studies on pregnant rat uteri in vitro

Anna Klukovits, Judit Verli, G. Falkay, R. Gáspár

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims: Previous results by our group showed that the in vitro uterus-relaxing potency of β2-adrenergic receptor (β2-AR) agonists and uterine cAMP accumulation are enhanced in case of visceral inflammation. Our aim was to study the effects of the non-selective phosphodiesterase (PDE) inhibitor theophylline and the selective PDE4 inhibitor rolipram on the uteri of intact late-pregnant female rats (on days 20 and 22 of pregnancy) and of pregnant rats treated with lipopolysaccharide (LPS) to evoke preterm labor (on day 20). Main methods: The effects of theophylline and rolipram alone and of rolipram with terbutaline were investigated in isolated organ system. Contractions were evoked with KCl. The forskolin- and terbutaline-stimulated cAMP accumulations were determined by enzyme immunoassay, with or without rolipram. Key findings: The maximum uterus-relaxing effects of theophylline and rolipram decreased significantly (p<0.05) with the progression of pregnancy in intact rats. The most pronounced effect of rolipram was detected in rats challenged with LPS on day 20. Rolipram increased the in vitro effect of terbutaline both in intact and in LPS-treated rats. In the presence of rolipram, the forskolin- and terbutaline-stimulated cAMP accumulations were higher in LPS-treated than in intact rats. Significance: The previous findings led us to conclude that the combined administration of PDE4 inhibitors with β2-agonists is of therapeutic value for the inhibition for uterine contractions, especially in the case of genital inflammation, which often triggers preterm birth. Combination therapy in general is associated with lesser side-effects, as a consequence of lower effective doses of each drug.

Original languageEnglish
Pages (from-to)733-737
Number of pages5
JournalLife Sciences
Volume87
Issue number23-26
DOIs
Publication statusPublished - Dec 18 2010

Fingerprint

Rolipram
Terbutaline
Phosphodiesterase Inhibitors
Uterus
Rats
Lipopolysaccharides
Theophylline
Phosphodiesterase 4 Inhibitors
Colforsin
Inflammation
Uterine Contraction
Pregnancy
Adrenergic Agonists
In Vitro Techniques
Premature Obstetric Labor
Premature Birth
Immunoenzyme Techniques
Personnel

Keywords

  • β-adrenergic receptor agonist
  • Genital inflammation
  • Phosphodiesterase 4 inhibitor
  • Preterm labor

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Improving the relaxing effect of terbutaline with phosphodiesterase inhibitors : Studies on pregnant rat uteri in vitro. / Klukovits, Anna; Verli, Judit; Falkay, G.; Gáspár, R.

In: Life Sciences, Vol. 87, No. 23-26, 18.12.2010, p. 733-737.

Research output: Contribution to journalArticle

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