Interactions between 8-L-arginine vasopressin and prostaglandin E2 in human mononuclear phagocytes

The effect of 8-L-arginine vasopressin (AVP) on biosynthesis of prostaglandins in human mononuclear phagocytes was examined. AVP, oxytocin, and deamino-(8-D-arginine) vasopressin (dDAVP) affected prostaglandin biosynthesis in a rank order that parallels their pressor but not antidiuretic activity (AVP greater than oxytocin greater than dDAVP). Radioimmunoassay, incorporation studies using [14C]arachidonic acid and radiometric thin-layer chromatography, revealed prostaglandin E2 (PGE2) to be the only prostaglandin synthesized by the mononuclear phagocytes. While high concentrations of PGE2 elevated cytoplasmic levels of cyclic AMP by five- to sevenfold above basal values, low concentrations of PGE2 that are released by the cells in the presence of AVP failed to increase cyclic AMP content in the cells. However, PGE2 at concentrations that do not alter cyclic AMP levels markedly interferes with the activity of AVP. This effect is, however, very time dependent. Addition of PGE2 to the cells 30 min before AVP, was followed by a period of unresponsiveness to the hormone that lasts at least 30 min. Pretreatment of the cells with indomethacin enhanced the AVP-mediated accumulation of intracellular cyclic AMP level. PGE2 did not modify [3H]AVP binding, indicating that its inhibitory effect on the activity of the peptide is not due to downregulation of vasopressin receptors.