Regional variations in contractile responses to prostaglandins and prostanoid receptor messenger ribonucleic acid in pregnant baboon uterus

OBJECTIVES: The aims of this study were to compare (1) the contractile responses of the lower uterine segment and fundus to prostaglandins, (2) expression of genes encoding prostanoid receptors in myometrium from different regions of the uterus, and (3) the distribution of expression of genes encoding prostanoid receptors (Preceptors) in key intrauterine tissues. STUDY DESIGN: Cesarean hysterectomy was performed in 8 pregnant baboons, not in labor, in the last third of pregnancy. Contractile responses of fresh tissue were quantified in a superfusion system. Polyadenylated ribonucleic acid was extracted from frozen tissue and gene expression was quantified by Northern blot analysis with complementary deoxyribonucleic acid probes. RESULTS: Prostaglandin E₂ contracted strips of myometrium from the fundus but had no significant effect on strips from lower uterine segment. Prostaglandin F(2α) contracted myometrium from both regions equally. Compared with fundus tissue, lower uterine segment tissue had greater expression of EP₂ receptor messenger ribonucleic acid, less expression of EP₃ receptor messenger ribonucleic acid, but similar levels of EP₄ receptor and FP receptor messenger ribonucleic acid. EP₂ receptor, EP₃ receptor, and EP₄ receptor messenger ribonucleic acids were also detected in cervix, decidua, and chorion. EP₂ receptor messenger ribonucleic acid was most abundant in the cervix, EP₃ receptor messenger ribonucleic acid was most abundant in the myometrium, and EP₄ receptor messenger ribonucleic acid was most abundant in the decidua. CONCLUSIONS: The reduced contractile response of lower uterine segment tissue to prostaglandin E₂ is paralleled by greater inhibitory EP₂ receptor expression and less contractile EP₃ receptor expression, a pattern similar to that seen in the cervix. Drugs with selective activity at prostanoid receptor types and subtypes are likely to allow safer and more effective control of the uterus and cervix than native prostaglandins.