Inflammatory processes enhance cAMP-mediated uterus relaxation in the pregnant rat: The role of TNF-α

Anna Klukovits, Árpád Márki, Eszter Páldy, Sándor Benyhe, Márta Gálik, George Falkay, Róbert Gáspár

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The objective of this study was to assess the in vitro uterus relaxing potency of β2-adrenergic receptor (β2-AR) agonists in pregnant rats after in utero administration of the bacterial lipopolysaccharide, Escherichia coli endotoxin (LPS). The LPS (100 μg/kg) was injected into the uterine lumen on day 16 of pregnancy. The effects of β2-AR agonist terbutaline was tested in vitro, in isolated uterine rings precontracted by electric field stimulation. Uterine β2-AR densities were detected by radioligand binding assay, the activated G-protein levels were investigated by a radiolabelled GTP binding assay. Uterine cAMP accumulation and the serum tumor necrosis factor-α (TNF-α) levels were measured by enzyme immunoassay. The endotoxin-evoked preterm delivery occurred on day 21. Higher pD2 values of terbutaline (p∈<∈0.001) were detected in endotoxin-treated rats: 9.14∈±∈0.36 vs. 7.71∈±∈0.12 compared with sham-operated rats. The densities or the equilibrium dissociation constants of β2-ARs were not different (p∈>∈0.05) in LPS-treated vs. control animals. Serum TNF-α level rose threefold after LPS treatment, but this rise was abolished by thalidomide. In LPS + thalidomide-treated rats, the effect of terbutaline became similar to that in sham-operated controls. By the measurement of myometrial cAMP levels, we documented that the concentration-response curve of terbutaline on cAMP accumulation was shifted to the left in the LPS-treated rats, with a significant rise in the pD2. We concluded that in the case of uterine inflammation, the in vitro uterus-relaxing potency of β2- agonists enhances, which is possibly mediated by TNF-α and uterine cAMP levels and that may serve as a rationale for the use of β2-AR agonists in the attenuation of preterm uterine contractions on an inflammatory basis.

Original languageEnglish
Pages (from-to)501-510
Number of pages10
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume379
Issue number5
DOIs
Publication statusPublished - May 1 2009

Keywords

  • Inflammation
  • Lipopolysaccharide
  • Preterm birth
  • TNF-α
  • cAMP
  • β-receptor agonists

ASJC Scopus subject areas

  • Pharmacology

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