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


METHODS
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, alpha,beta-methylene-ATP (alpha,beta-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 x 10(-4) M), alpha,beta-meATP (10(-7) to 3 x 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 alpha,beta-meATP and EFS was higher in full term pregnancy than in earlier pregnancy. PPADS antagonized uterus responses to alpha,beta-meATP and EFS, but not to ATP, in all three groups.


CONCLUSIONS
P2X receptor-mediated contractions of human pregnant uterus to alpha,beta-meATP and EFS, but not to ATP, are increased with the progression of pregnancy.
Ziganshin
Airat U
AU
Department of Pharmacology, Pharmacognozy and Botany, Kazan State Medical University, 49 Butlerov Street, Kazan 420012, Russia. airatziganshin@yahoo.co.uk
Zaitcev
Alexander P
AP
Khasanov
Albir A
AA
Shamsutdinov
Airat F
AF
Burnstock
Geoffrey
G
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects*; D011247:Pregnancy / Q000502:physiology*; D011262:Pregnancy Trimester, Second / Q000502:physiology; D011263:Pregnancy Trimester, Third / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D015854:Up-Regulation / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*
D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate