Potentiation of uterine effects of prostaglandin F2{alpha} by adenosine 5'-triphosphate.
OBJECTIVE
To investigate the interaction of exogenous adenosine 5'-triphosphate (ATP), a P2 receptor agonist, with prostaglandin F(2alpha) (PGF(2alpha)) on pregnant women in labor as well as on isolated human pregnant uterus preparations.


METHODS
For an in vitro study, myometrial samples were obtained from 27 women undergoing elective cesarean delivery at term. Concentration-response relationships for ATP (10(-8) -3 x 10(-4) mol/L), PGF(2alpha) (10(-9) -10(-5) mol/L), and their combination were obtained by using routine pharmacological organ bath technique. An in vivo study was performed with 34 pregnant women with dysfunctional abnormalities of the active stage of labor who were randomly allocated into 2 study groups. The women in the control group (18 patients) received intravenous prostaglandin F(2alpha) at an initial rate of 7.5 mug/min, whereas the women in the ATP group (16 patients) received prostaglandin F(2alpha) concomitantly with ATP (0.45 nmol/min, intravenously).


RESULTS
Adenosine 5'-triphosphate at concentrations of 10(-6) -3 x 10(-4) mol/L and PGF(2alpha) at concentrations of 10(-8) -10(-5) mol/L caused concentration-dependent contractions of isolated smooth muscle preparations of the human pregnant uterus. At concentrations of 10(-6) mol/L and below, ATP had no effects on mechanical activity of the isolated uterus, but at concentrations of 10(-7) mol/L and 10(-6) mol/L, it significantly potentiated the contractile responses of the uterus induced by PGF(2alpha) (P < .05, 2-way analysis of variance). Patients receiving intravenous infusion of ATP as a supplement to PGF(2alpha) treatment, compared with those without ATP, had a significantly shorter interval from the start of the treatment to full cervical dilatation (3.31 +/- 1.49 hours and 4.67 +/- 1.11 hours in ATP and control groups, respectively; P = .014, Wilcoxon Mann-Whitney test). The total dose of prostaglandin received was significantly lower in the ATP group than that of controls (1,489.8 +/- 699.9 mug and 3,394.2 +/- 1,951.9 mug, respectively; P = .003, Wilcoxon Mann-Whitney test). No side effects of ATP treatment were observed during or after infusion.


CONCLUSIONS
Adenosine 5'-triphosphate potentiates effects of PGF(2alpha) on pregnant human uterus in vitro and in vivo and thus could be a useful supplemental drug to increase uterine contractility at labor.
Ziganshin
Airat U
AU
Department of Pharmacology, Kazan State Medical University, Kazan, Russia. airatziganshin@yahoo.co.uk
Zefirova
Julia T
JT
Zefirova
Tatiana P
TP
Ziganshina
Lilia E
LE
Hoyle
Charles H V
CH
Burnstock
Geoffrey
G
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology*; D015237:Dinoprost / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D011247:Pregnancy; D058910:Purinergic P2 Receptor Agonists; D014590:Uterine Contraction / Q000187:drug effects; D014593:Uterine Inertia / Q000188:drug therapy*; D014599:Uterus / Q000187:drug effects*
D058910:Purinergic P2 Receptor Agonists; D000255:Adenosine Triphosphate; D015237:Dinoprost