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© Copyright 2004 The British Pharmacological Society

060P University of Bath
Summer Meeting July 2004

Pharmacological characterisation of purine receptors in pregnant rat uterus

S. Ali, J. Bains, B. Burmi, H. Mistry, R. J. Carson. Physiology Section, School of Science & the Environment, Coventry University

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Ali S
Bains J
Burmi B
Mistry H
Carson RJ

The control of uterine contractility during pregnancy and labour is not fully understood. It is not clear whether purinergic receptor agonists have a role in controlling contractility of the pregnant uterus. A1 and A2 receptors have been reported in the pregnant and non-pregnant Guinea-pig myometrium (Smith et al., 1988; Schiemann & Buxton, 1991; Haynes & Pennefather, 1993). A and P2 receptors have been reported in the non-pregnant rat uterus (Gillman & Pennefather, 1998). Evidence for a contractile effect of P2 agonists has been reported in pregnant human myometrium (Ziganshin et al., 2002). The aim of the study was to investigate the effects of purinergic agonists and antagonists on isolated pregnant rat uterus.

Uterine strips from young adult female Wistar rats at 19 days of gestation were set up in organ baths at 37 °C, bathed in Krebs buffer and gassed with 95% O2/5% CO2. Spontaneous contractions were recorded via a force transducer and a Powerlab computer set up (AD Instruments). Tissues were allowed to equilibrate for 1 hour and were then exposed to a dose of 45 mM KCl to induce a reference full contraction. A dose range of adenosine, ATP, ADP and UTP of 10-9 - 5 x 10-4 M was applied to the tissue (n = 10 for each agonist). Time-matched controls (n = 10) were run simultaneously using Krebs buffer vehicle. Spontaneous contractions were recorded for 10 minutes post dose. Amplitude, frequency, baseline tone and integral of the contractions over ten minute periods were analysed. The integral was expressed as a percentage of the initial integral of the contraction due to KCl. The experiments were repeated in the presence of antagonists: reactive blue 2 (P2 antagonist), MRS 1191 (A3 antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (A1 antagonist) (n = 5), and using a selective P2X agonist: , ß - methylene ATP (n = 5). Data were analysed by ANOVA with a post hoc test.

ATP significantly increased the amplitude of spontaneous contractions (P<0.05) and significantly decreased the frequency of contractions (P<0.05), compared to control, and this action was inhibited by reactive blue 2. , ß - methylene ATP significantly decreased frequency of contraction and there was a trend to increase amplitude with increasing dose, but this did not reach significance. This suggests the functional expression of P2X receptors in pregnant rat uterus. UTP and ADP did not significantly affect contractility, compared to control, suggesting a lack of expression or activity of P2Y receptors. Adenosine significantly decreased the frequency of contraction (P<0.04), which was inhibited by MRS 1191, but not by xanthine. This suggests the presence of adenosine receptors in pregnant rat uterus. In the presence of MRS1191, adenosine caused an increasing trend in amplitude with dose, which reached significance at the highest dose of 5x10-4 M. In conclusion, the results suggest that A and P2X receptors, but not P2Y receptors are expressed in pregnant rat uterus.

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Schiemann W.P. & Buxton I.L. (1991) Am. J. Physiol. 261, E665-672
Smith M.A. et al. (1988) J. Pharmacol. Exp. Ther. 247, 1059-1063
Ziganshin A.U. et al. (2002) Bull. Exp. Biol. Med. 133, 255-257