Oxytocin receptors and prostaglandin release in rabbit amnion

Besides stimulating uterine myometrial and mammary myoepithelial cell contraction, oxytocin (OT) causes the release of prostaglandins (PGs) from uterine endometrium/decidua and amnion cells. Lacking information about OT receptors eliciting PG release, we don't know how they are related to OT receptors involved in smooth muscle contraction. The amnion offers great potential for characterizing OT receptors associated with PG release, as the amount of iodinated OT antagonist ([125I]OTA) bound to rabbit amnion membranes during labor is among the greatest of any tissue yet studied, reaching about 10 pmol/mg membrane protein. The relative affinities of several OT analogues for binding sites on amnion membranes are the same as those on decidual membranes. There are differences in the ligand profile between amnion and myometrium, but they could be due to the additional presence of vasopressin receptors on myometrial membranes. An increase in the sensitivity of PGE2 release from amnion cells in culture to OT and analogues accompanies the rise in OT receptor concentration at the end of gestation. Increases in [125I]OTA binding in vivo can be mimicked with cultured amnion cells by addition of agents that elevate intracellular cAMP levels. Based on the time course and inhibition of the increase with cycloheximide, cAMP might induce OT receptor gene expression. The increase also is reflected by a marked elevation in the covalent labeling of a 50-kDa electrophoretic band with a photoactivated derivative of [125I]OTA. Because of the homogeneity of cell types in the amnion, the ease of culturing amnion cells, and the high concentration of OT receptors that can be induced, this tissue should be very useful in characterizing OT receptors associated with PG synthesis.