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

Abstract

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 myo-metrium from different regions of the uterus, and (3) the distribution of expression of genes encoding prostanoid receptors (P receptors) in key intrauterine tissues. 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. Prostaglandin E2 contracted strips of myometrium from the fundus but had no significant effect on strips from lower uterine segment. Prostaglandin F2 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 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. 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.