Cellular mechanisms by which oxytocin stimulates uterine PGF2 alpha synthesis in bovine endometrium: roles of phospholipases C and A2.

The objective of these experiments was to identify the cellular mechanisms by which oxytocin stimulates prostaglandin (PG) F2 alpha synthesis in bovine endometrial tissue. Uteri were collected on the day after spontaneous luteal regression. Caruncular endometrial explants were dissected and incubated in vitro to assess PGF2 alpha release or phospholipase (PL) C activity. Oxytocin (10(-6) M) stimulated PGF2 alpha release and PLC activity within 30 min of incubation (P < 0.01). The highest stimulation was observed at 100 min (P < 0.01). Oxytocin stimulated PLC activity at 10(-9) M and higher doses, whereas an increase in PGF2 alpha release was not detected until 10(-8) M (P < 0.09). Melittin, a stimulator of PLA2 activity, stimulated PGF2 alpha release at 10(-6) M and higher doses (P < 0.01). Aristolochic acid, an inhibitor of PLA2 activity, blocked the ability of oxytocin to stimulate PGF2 alpha release at 10(-5) M and higher doses (P < 0.01). Aristolochic acid (10(-4) M) reduced the stimulation of PGF2 alpha release induced by A1F4-, a nonspecific stimulator of G protein (10(-5) M) and melittin (10(-4) M; P < 0.05). Aristolochic acid had no effect on the ability of oxytocin or A1F4- to stimulate PLC activity (P > 0.10). By comparing the time course of stimulation and dose-response relationships between PGF2 alpha and PLC activity, it appears that oxytocin may stimulate PGF2 alpha secretion by activating PLC. The effects of melittin and aristolochic acid indicate that PLA2 may play a role in mediating the stimulatory effect of oxytocin on PGF2 alpha secretion, as well.