This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gáspár, R. Articles by Falkay, G. Search for Related Content PubMed PubMed Citation Articles by Gáspár, R. Articles by Falkay, G.

Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone

¹ Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary, ² Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt. 62, Hungary and ³ Department of Obstetrics and Gynecology, Faculty of Medicine, University of Szeged, WHO Collaborating Research Center in Human Reproduction, H-6725 Szeged, Semmelweis u. 1, Hungary

Correspondence should be addressed to George Falkay; Email: falkay{at}pharma.szote.u-szeged.hu

The effectiveness of ß₂-agonists in preterm delivery is reduced by several factors. The aim of this study was to determine the influence of late pregnancy in the uterus-relaxing effect of terbutaline in the rat in vitro.

Rat uterine tissues from late pregnancy (days 15, 18, 20 and 22) were used. In vitro electrical field-stimulation (EFS) was used to evoke contractions. The radioligand-binding technique, reverse transcription-polymerase chain reaction and radioimmunoassay technique were used to determine the ß-adrenergic receptor density and mRNA level and the plasma sex hormone level, respectively. The activated G-protein level of the ß-adrenergic receptors was investigated by a radiolabelled GTP binding assay.

EFS-induced contractions were inhibited by terbutaline. This effect decreased towards term with respect to both the EC₅₀ and maximal inhibition values. A drop in plasma progesterone level was also detected. Binding studies revealed an increase in ß-adrenergic receptor number on the last day of pregnancy, which correlated with the change in receptor mRNA level. The G-protein-activating effect of terbutaline decreased continuously between days 15 and 20. Surprisingly, terbutaline decreased the G-protein activation to below the basal level on day 22. However, progesterone pretreatment set back the uterine action of terbutaline, increased the density of the ß₂-adrenergic receptors and their mRNA level and increased the G-protein-activating property of terbutaline.

These data provide evidence of a pregnancy-induced decrease in activated G-protein level after ß₂-agonist stimulation. The decrease in plasma progesterone level has a crucial role in this process. The effects of ß₂-adrenergic receptor agonists in tocolytic therapy may possibly be potentiated with progesterone.