Endocrine Abstracts

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 (K_ATP 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 (K_ATP 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 (K_ATP 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 K_ATP 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 K_ATP channel density and β₂-adrenoceptor induced K_ATP channel activation in the rat myometrium.

Results of our study evidently suggest the functional presence of K_ATP 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 K_ATP 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).