Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 31 P300 | DOI: 10.1530/endoabs.31.P300

SFEBES2013 Poster Presentations Pituitary (71 abstracts)

KATP channels are involved in the tocolytic effect of β2 agonists in pregnant rat

Norbert Lovasz , Andrea Koncz , Eszter Ducza & George Falkay


Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged/Csongrad, Hungary.


Preterm birth defined is a major determinant of neonatal mortality and morbidity. The incidence of preterm birth has not decreased over the years despite major improvements in medical research. In the view to decreasing the potentially maternal and foetal adverse events it is a pharmacological challenge to find new therapeutic strategies. In the clinical practice the most frequently used tocolytic agents are the β2-adrenoceptor agonist (terbutaline, fenoterol, ritodrine).

Present study unravels the functional presence of ATP-sensitive potassium channel (KATP channel) and its involvement in mediating β2-adrenoceptors-induced myometrial relaxation in rat myometrium at 6 and 22 days of gestation. The tissues pretreated with 10−6 M glibenclamide (KATP channel blocker), the relaxant effect of β2 agonists were significantly lower compared with alone and the dose-response curves were shifted to right at day 6 of pregnancy, while the glibenclamide was ineffective at day 22. The combination of β2 agonists with pinacidil (KATP channel opener) the uterus-relaxant effect dose-dependently increased at day 6 of pregnancy. At term the synergism between β2 agonists and pinacidil was not observed. The ontogeny of KATP channel subunit (SUR1) was investigated by RT-PCR and western blot techniques; high level was found at 6 day of pregnancy and low level was detected at term. From these results it can be concluded: there is a close correlation between KATP channel density and β2-adrenoceptor induced KATP channel activation in the rat myometrium.

Results of our study evidently suggest the functional presence of KATP channel in the pregnant rat myometrium and the role of β2-adrenoceptor agonist induced myometrial relaxation at early stage of pregnancy. Based on these findings, it may not be suggest that the therapeutic application of both the β2-adrenoceptor agonist and specific KATP channel opener as promising tocolytic agent. However, it may be used for treatment of habitual abortion.

Declaration of funding: This work was supported by the New Hungary Development Plan (TÁMOP-4.2.1/B-09/1/KONV-2010-0005 – Creating the Center of Excellence at the University of Szeged).

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