Cellular mechanisms by which oxytocin stimulates uterine PGF(2 alpha) synthesis in bovine endometrium: Roles of phospholipases C and A(2)

The objective of these experiments was to identify the cellular mechanisms by which oxytocin stimulates prostaglandin (PG) F-2 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 PGF(2 alpha) release or phospholipase (PL) C activity. Oxytocin (10(-6) M) stimulated PGF(2 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 PGF(2 alpha) release was not detected until 10(-8) M (P < 0.09). Melittin, a stimulator of PLA(2) activity, stimulated PGF(2 alpha) release at 10(-6) M and higher doses (P < 0.01). Aristolochic acid, an inhibitor of PLA(2) activity, blocked the ability of oxytocin to stimulate PGF(2 alpha) release at 10(-5) M and higher doses (P < 0.01). Aristolochic acid (10(-4) M) reduced the stimulation of PGF(2 alpha) release induced by AlF4-, 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 AlF4- to stimulate PLC activity (P > 0.10). By comparing the time course of stimulation and dose-response relationships between PGF(2 alpha) and PLC activity, it appears that oxytocin may stimulate PGF(2 alpha) secretion by activating PLC. The effects of melittin and aristolochic acid indicate that PLA(2) may play a role in mediating the stimulatory effect of oxytocin on PGF(2 alpha) secretion, as well. (C) Elsevier Science Inc. 1997.