ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 12 P106

Preliminary investigation on the effects of prostaglandin EP2 and EP4 agonists on isolated uterus from non-pregnant and pregnant mice

AL Griffiths1, KM Marshall1, J Senior1 & DF Woodward2

1University of Bradford, Bradford, United Kingdom; 2Allergan, California, United States.

The aim of this study was to compare the effects of prostaglandin EP2 – and EP4 -receptor agonists on uterine tissue taken from non-pregnant and pregnant mice.

Uterine tissue was taken from non-pregnant animals during dioestrus and from pregnant animals on day 18 of gestation. Samples were set-up for superfusion (Krebs’ solution with 1 μM indometacin at 2 ml/min and 37 °C) as previously described by Senior et al. (1991). 1 μM 5-HT was added to the Krebs’ solution to maintain myogenicity. After 30-minute equilibration, the EP2 (butaprost, AH13205 and CP533536) and EP4 (AGN197564, AGN201734, AGN211330 and PDA124) agonists were administered directly into the superfusate as bolus doses, immediately after a contraction. Responses were measured as length of time of inhibition and were also expressed as a percentage of 5 minutes of hypotonic shock. Data was statistically analysed using a two-way ANOVA and Bonferroni post hoc test.

With the exception of CP533536 at 10−7mols none of the EP2 agonists tested inhibited uterine activity. AH13205 evoked excitation at the highest dose (10−7 mols) in non-pregnant tissue. The EP4 agonists tested inhibited activity only in tissues taken from non-pregnant animals. PDA124 exhibited the greatest inhibition and the rank order of inhibitory effectiveness was as follows: PDA124 > AGN201734 > AGN197564 > AGN21130. Excitation was observed at the higher doses of AGN197564 and AGN211330.

The data suggest that there is a population of functional EP4 receptors, which mediate spasmogenolysis, on the non-pregnant mouse uterus but this population diminishes at late gestation. These results imply that there is a paucity of EP2 receptors on the non-pregnant and pregnant mouse uterus. The initial excitation observed with some of the compounds tested in this study could be mediated via excitatory EP receptors and this is currently being investigated.

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