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FACTORS AFFECTING PROSTACYCLIN FORMATION BY THE RAT PREGNANT MYOMETRIUM
Author(s) -
TAHIR K.E.H.,
WILLIAMS K.I.
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb10985.x
Subject(s) - prostacyclin , myometrium , incubation , arachidonic acid , chemistry , prostaglandin , microgram , endocrinology , medicine , chromatography , tranylcypromine , uterus , biochemistry , enzyme , in vitro , monoamine oxidase
1 The scraped myometrium of the pregnant uterus of the rat, when chopped and incubated, released an antiaggregatory material closely resembling prostacyclin (PGI 2 ). The material was conclusively identified as PGI 2 by identification of its hydrolysis product 6‐oxo‐prostaglandin F 1α (6‐oxo‐PGF 1α ) by gas chromatography‐mass spectrometry (GC‐MS). 2 Peak concentrations of PGI 2 were detected after 15 min incubation at 20°C. These concentrations were significantly higher than those detected at 37°C, when largest amounts of prostacyclin were formed after 3 min incubation. The concentrations of 6‐oxo‐PGF 1α detected were similar at the different temperatures. 3 When samples were incubated at pH 8 and 20°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 A 2 stimulated prostacyclin production. 5 Preincubation of myometrial tissue for 10 min at 37°C with inhibitory drugs before chopping reduced prostacyclin output. The doses needed to reduce PGI 2 output by 50% (ID 50 ) were: mepacrine (280 μg/ml), indomethacin (20 μg/ml), 5,8,11,14 eicosatetraynoic acid (23 μg/ml), 15‐hydroperoxy arachidonic acid (23 μg/ml) and tranylcypromine (225 μg/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.