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 resp onses of the lower uterine segment and fundus to prostaglandins, (2) expres sion of genes encoding prostanoid receptors in myometrium from different re gions of the uterus, and (3) the distribution of expression of genes encodi ng prostanoid receptors (P receptors) in key intrauterine tissues. STUDY DESIGN: Cesarean hysterectomy was performed in 8 pregnant baboons, no t 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 E-2 contracted strips of myometrium from the fundus but had no significant effect on strips from lower uterine segment. Prostag landin F-2 alpha 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 me ssenger ribonucleic acid, but similar levels of EP4 receptor and FP recepto r messenger ribonucleic acid. EP2 receptor, EP3 receptor, and EP4 receptor messenger ribonucleic acids were also detected in cervix, decidua, and chor ion. EP2 receptor messenger ribonucleic acid was most abundant in the cervi x, EP3 receptor messenger ribonucleic acid was most abundant in the myometr ium, and EP4 receptor messenger ribonucleic acid was most abundant in the d ecidua. CONCLUSIONS: The reduced contractile response of lower uterine segment tiss ue to prostaglandin E-2 is paralleled by greater inhibitory EP2 receptor ex pression and less contractile EP3 receptor expression, a pattern similar to that seen in the cervix. Drugs with selective activity at prostanoid recep tor types and subtypes are likely to allow safer and more effective central of the uterus and cervix than native prostaglandins.