title: Prostacyclin biosynthesis by cultured human myometrial smooth muscle cells: dependency on arachidonic or linoleic acid in the culture medium.
abstract: Myometrial smooth muscle cells in culture were incubated for 18 hours in medium that contained serum (10%); under these conditions, there was a six to 26-fold increase in the amount of 6-keto-prostaglandin F1 alpha that accumulated in the medium (i.e., prostacyclin production) compared with that present after incubation in serum-free medium. In serum-free and serum-containing media, treatment of these cells with dexamethasone (10(-8) mol/L) or cortisol (10(-7) mol/L) suppressed the biosynthesis of prostacyclin by approximately 80% and 64%, respectively. Arachidonic acid (bound to fatty acid-free human serum albumin) added to serum-free medium caused a concentration-dependent increase in the production of prostacyclin by myometrial cells. Arachidonic acid was maximally effective at a concentration of 10(-5) mol/L and caused a five- to 28-fold increase in the biosynthesis and secretion of prostacyclin. Linoleic acid (bound to albumin) in serum-free medium also caused a concentration-dependent increase in the production of prostacyclin; however, the amount of prostacyclin produced in the presence of linoleic acid was lower than that produced in the presence of an equimolar concentration of arachidonic acid. In the presence of arachidonic (10(-5) mol/L) or linoleic acids (10(-4) mol/L) in serum-free medium, the addition of dexamethasone (10(-8) mol/L) or cortisol (10(-7) mol/L) suppressed but did not inhibit completely prostacyclin production. These findings are indicative that arachidonic and linoleic acids in the culture medium support prostacyclin biosynthesis by human myometrial smooth muscle cells. The inhibition of prostacyclin production by glucocorticosteroids in the absence or presence of extracellular arachidonic (or linoleic) acid may be caused by inhibition of phospholipase A2 activity.
authors.affiliation: Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9051.
authors.forename: L W
authors.initials: LW
authors.lastname: MacKenzie
authors.forename: P C
authors.initials: PC
authors.lastname: MacDonald
authors.forename: L
authors.initials: L
authors.lastname: Milewich
authors.forename: M L
authors.initials: ML
authors.lastname: Casey
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D003470:Culture Media; D005938:Glucocorticoids; D008041:Linoleic Acids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D019787:Linoleic Acid; D011464:Epoprostenol