Up-regulation of oxytocin receptors in rabbit amnion by adenosine 3',5'-monophosphate.

The marked up-regulation of oxytocin (OT) receptors in rabbit amnion at term was reproduced in cultured amnion cells by raising intracellular cAMP levels. (Bu)2AMP, forskolin, or cholera toxin caused 2- to 8-fold increases in specific binding of iodinated OT antagonist. The rise in OT receptors involves activation of protein kinase-A activity and protein synthesis, as forskolin's effects were inhibited by H-7 and H-8 and by cycloheximide, respectively. Forskolin treatment also increased specific cross-linking of a photoaffinity derivative of [125I]OT antagonist to a 50-kilodalton electrophoretic band corresponding in size to the amnion OT receptor. Forskolin and (Bu)2cAMP increased OT stimulation of prostaglandin E2 (PGE2) release; PGE2 release elicited by epidermal growth factor or calcium ionophore was unchanged. Forskolin also enhanced stimulation of PGE2 synthesis by phorbol 12-myristate 13-acetate, an activator of protein kinase-C. Because protein kinase-C mediates OT action in amnion cells, forskolin causes increases in both the signal and signal transduction mechanisms. These results suggest that cAMP mediates the exponential-like rise in rabbit amnion OT receptors occurring in vivo at term. The physiological signals increasing cAMP concentrations in amnion may be important for OT stimulation of PGE2 release and, therefore, have a significant role in the initiation and/or progression of labor.