Term-dependency of P2 receptor-mediated contractile responses of isolated human pregnant uterus

Abstract

Objective The aim of the study was to test the hypothesis that in the human uterus, the effectiveness of P2 receptor-mediated contractile responses is up-regulated during pregnancy. Study design Experiments were performed on myometrial samples obtained from women undergoing caesarean section at 28–30 weeks of pregnancy (3 women, Group 1), 32–34 weeks of pregnancy (6 women, Group 2) and 38–41 weeks of pregnancy (16 women, Group 3). Concentration–response relationships for a non-selective P2 receptor agonist, adenosine 5′-triphosphate (ATP), a selective P2X receptor agonist, α,β-methylene-ATP (α,β-meATP), and a frequency–response relationship for non-adrenergic non-cholinergic (NANC) electrical field stimulation (EFS) were obtained using routine pharmacological organ bath technique. Effects of pyridoxalphosphate azophenyl-2′,4′-disulphonic acid (PPADS, 10 −5 M), a P2 receptor antagonist, were also evaluated. Parametric Student's t-test, non-parametric Wilcoxon T-test, Mann–Whitney U-test, two-way analysis of variance (ANOVA) and Krushkal–Wallis tests were used for statistical analysis. Results ATP (10 −6 to 3 × 10 −4 M), α,β-meATP (10 −7 to 3 × 10 −5 M) and EFS (2–32 Hz) evoked contractions of isolated pregnant uterus in all three groups. Uterus responses to ATP were not correlated with the term of pregnancy while the amplitude of uterine contractions to α,β-meATP and EFS was higher in full term pregnancy than in earlier pregnancy. PPADS antagonized uterus responses to α,β-meATP and EFS, but not to ATP, in all three groups. Conclusion P2X receptor-mediated contractions of human pregnant uterus to α,β-meATP and EFS, but not to ATP, are increased with the progression of pregnancy.