Factors affecting prostacyclin formation by the rat pregnant myometrium.

Abstract

1 The scraped myometrium of the pregnant uterus of the rat, when chopped and incubated, released an antiaggregatory material closely resembling prostacyclin (PGI2). The material was conclusively identified as PGI2 by identification of its hydrolysis product 6-oxo-prostaglandin F12 (6-oxo-PGF1 alpha) by gas chromatography-mass spectrometry (GC-MS). 2 Peak concentrations of PGI2 were detected after 15 min incubation of 20 degrees C. These concentrations were significantly higher than those detected at 37 degrees C, when largest amounts of prostacyclin were formed after 3 min incubation. The concentrations of 6-oxo-PGF1 alpha detected were similar at the different temperatures. 3 When samples were incubated at pH 8 and 20 degrees C, peak concentrations of prostacyclin were maintained between 15 and 35 min of incubation. When pH 7.4 was employed, prostacyclin concentration in the incubate fell to undetectable limits within this time. 4 Incubation of the chopped myometrium with arachidonic acid or phospholipase A2 stimulated prostacyclin production. 5 Preincubation of myometrial tissue for 10 min at 37 degrees C with inhibitory drugs before chopping reduced prostacyclin output. The doses needed to reduce PGI2 output by 50% (ID50) were: mepacrine (280 micrometer/ml), indomethacin (20 microgram/ml), 5,8,11,14 eicosatetraynoic acid (23 microgram/ml), 15-hydroperoxy arachidonic acid (23 microgram/ml) and tranylcypromine (225 microgram/ml). 6 It is suggested that due to the large amounts of material available, the rat pregnant myometrium is a useful model for the study of factors affecting prostacyclin synthesis.