Evidence that Platelet-Activating Factor Suppresses Uterine Oxytocin-Induced 13, 14-Dihydro-15-Keto-Prostaglandin F2α Release and Phosphatidylinositol Hydrolysis in the Ewe1

Abstract

This study was conducted to determine whether platelet-activating factor (PAF) (1) attenuated oxytocin-induced secretion of the prostaglandin (PG) F2 alpha metabolite, PGFM, by the ovine uterus in situ and (2) inhibited the generation of the inositol phosphate secondary messengers by endometrial tissue in response to oxytocin challenge in vitro. Ovariectomized ewes received steroid replacement to mimic the luteal phase. Six ewes received intrauterine injections of 200 micrograms PAF/uterine horn/day on Days 11-15, and 6 ewes were treated with vehicle. All ewes received 1 microgram oxytocin i.v. on Days 13-16. Pretreatment of ewes with PAF significantly suppressed PGFM release in response to oxytocin on Days 14 and 15 (p less than 0.005) compared to vehicle-treated ewes. PAF was not administered on Day 16, and the PGFM response to oxytocin was not different between groups. In a second experiment, ewes were given intrauterine injections of 200 micrograms PAF/uterine horn/day (n = 8) or vehicle (n = 7) on Days 11-15, and all ewes received 1 microgram oxytocin i.v. on Days 13 and 14. On Day 15 the uterus was removed, and the incorporation of 3H-inositol into inositol phosphates was determined in caruncular endometrium. Treatment of ewes with PAF in vivo reduced inositol monophosphate (IP1) generated by oxytocin (10(-6) M) by 56.4%, compared to that in endometrium from vehicle-treated controls, and also inhibited the incorporation of 3H-inositol into glycerophosphoinositol (GPI). If PAF was added to the endometrium during the incubation in vitro, the attenuation of inositol phosphate generation did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Components of a platelet-activating factor-signaling loop are assembled in the ovine endometrium late in the estrous cycle

“…The mobilization of polyphosphated inositols in ovine endometrium by PAF treatment is consistent with this receptor being functional in this tissue (3). The sex hormone dependency of the PAF receptor expression (Fig.…”

“…However, the rapid action of PAF on the endometrium suggests that its effects may be primarily nongenomic. PAF is known to activate phospholipase A 2 in several cell types (3,17,22), and such action in the uterus may free arachidonic acid for PG synthesis (31).…”

“…The PAF receptor detected in the endometrium is a G protein-coupled receptor that is capable of linking to a range of effectors, including phospholipase A 2 (3,17,22) and phospholipase C (12,34). The mobilization of polyphosphated inositols in ovine endometrium by PAF treatment is consistent with this receptor being functional in this tissue (3).…”

“…It was shown (4) that the production and release of plateletactivating factor (PAF, 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine) by the ovine endometrium in ovariectomized ewes were regulated by estradiol and progesterone and that the uterus of such animals responded to PAF infusion with a pulse-like release of PGF 2␣ measured as its stable metabolite (PGFM) (3). However, it is yet to be shown whether PAF is produced at the time of initiation of luteolysis in the normal estrous cycle or whether a PAF receptor is expressed in endometrial tissue at the time it is required to respond to PAF.…”

Oxytocin- and aluminium fluoride-induced phospholipase C activity and prostaglandin F2 secretion during the ovine luteolytic period

“…The failure to detect significant stimulation of PLC activity or PGF2a synthesis on day 14 after oestrus is difficult to explain, particularly when stimulation was detected on days 13 and 15 in the present study and has been observed on day 14 in a previous study (Silvia and Raw, 1993 (Battye et al, 1992 (Miller et al, 1977 …”