Endocrine Abstracts

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.