CELLULAR MECHANISMS BY WHICH OXYTOCIN STIMULATES UTERINE PGF(2-ALPHA)SYNTHESIS IN BOVINE ENDOMETRIUM - ROLES OF PHOSPHOLIPASE-C AND A(2)

The objective of these experiments was to identify the cellular mechan isms by which oxytocin stimulates prostaglandin (PG) F-2 alpha synthes is in bovine endometrial tissue. Uteri were collected on the day after spontaneous luteal regression. Caruncular endometrial explants were d issected and incubated in vitro to assess PGF(2 alpha) release or phos pholipase (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 stimu lated PLC activity at 10(-9) M and higher doses, whereas an increase i n PGF(2 alpha) release was not detected until 10(-8) M (P < 0.09). Mel ittin, a stimulator of PLA(2) activity, stimulated PGF(2 alpha) releas e at 10(-6) M and higher doses (P < 0.01). Aristolochic acid, an inhib itor 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). Aristolo chic acid (10(-4) M) reduced the stimulation of PGF(2 alpha) release i nduced 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 relationshi ps between PGF(2 alpha) and PLC activity, it appears that oxytocin may stimulate PGF(2 alpha) secretion by activating PLC. The effects of me littin and aristolochic acid indicate that PLA(2) may play a role in m ediating the stimulatory effect of oxytocin on PGF(2 alpha) secretion, as well. (C) Elsevier Science Inc. 1997.