RESUMEN
To investigate whether female sex hormones and pregnancy induce increased gallbladder synthesis of prostaglandin I2 (PGI2) and prostaglandin E (PGE), we used an in vitro incubation chamber to quantitate the effects of progesterone, estrogen, pregnancy, and pregnancy plus a 2%-cholesterol diet on mucosal and serosal PGI2 and PGE production by the rabbit gallbladder. Neither the female sex hormones nor pregnancy alone caused a significant increase in PGI2 or PGE synthesis. The gallbladders of cholesterol-fed, pregnant rabbits demonstrated significant increases only in serosal synthesis of PGI2. This increased production was equivalent to that noted for gallbladders from nonpregnant rabbits fed a high-cholesterol diet. There were no increases in mucosal synthesis of PGE or of PGI2. Thus, neither elevated levels of progesterone or estrogen nor pregnancy is directly responsible for the increased PGI2 activity in the female gallbladder; conversely, this effect seems to be mediated by the increased biliary concentrations of cholesterol.
Asunto(s)
Vesícula Biliar/metabolismo , Hormonas Esteroides Gonadales/farmacocinética , Preñez/metabolismo , Prostaglandinas E Sintéticas/biosíntesis , Prostaglandinas E/biosíntesis , Prostaglandinas F Sintéticas/biosíntesis , Animales , Ácidos Araquidónicos/farmacocinética , Bilis/análisis , Colelitiasis/metabolismo , Colesterol/sangre , Colesterol/farmacocinética , Dinoprostona , Estradiol/farmacología , Estrógenos/sangre , Estrógenos/farmacocinética , Femenino , Hormonas Esteroides Gonadales/sangre , Humanos , Técnicas In Vitro , Embarazo , Progesterona/sangre , Progesterona/farmacocinética , Conejos , RadioinmunoensayoRESUMEN
Human umbilical vein endothelial cells were found to contain adrenic acid (22:4) in their cellular lipids. Since this fatty acid may be metabolized by cyclooxygenase in the kidney, the metabolism of adrenic acid was studied in endothelial cell cultures. [14C]Adrenic acid was metabolized to several more polar metabolites. Two of these metabolites co-migrated on HPLC with 1 alpha,1 beta-dihomo-8-ketoprostaglandin F1 alpha (the metabolite of 1 alpha, 1 beta-dihomoprostaglandin I2) and 1 alpha,1 beta-dihomoprostaglandin E2. Indomethacin (10(-5) M) inhibited the synthesis of these metabolites. When cells were treated with adrenic acid (3 X 10(-5) M), a peak that co-migrated with dihomo-8-ketoprostaglandin F1 alpha was detected by radioimmunoassay using an antiserum directed against 6-ketoprostaglandin F1 alpha. The presence of dihomo-8-ketoprostaglandin F1 alpha was confirmed by gas chromatography-mass spectrometry. Immunoreactive peaks that co-migrated with dihomoprostaglandins E2 and F2 alpha were identified with antisera against prostaglandin E2 and prostaglandin F2 alpha, respectively. [14C]Arachidonic acid was metabolized to [14C]prostaglandin F2 alpha, 6-keto[14C]prostaglandin F1 alpha, and [14C]prostaglandin E2. Similar results were found with unlabelled arachidonic acid using specific antisera. When the two fatty acids were combined, adrenic acid reduced the metabolism of arachidonic acid. The culture media from endothelial cells inhibited thrombin-induced platelet aggregation, an effect blocked by aspirin. The inhibitory activity of the media was enhanced when arachidonic acid was added to the cells, but it was reduced by adrenic acid. Both prostaglandin I2 and dihomoprostaglandin I2 inhibited platelet aggregation, but prostaglandin I2 was 100-times more potent. We conclude that adrenic acid is metabolized in human endothelial cells to 1 alpha, 1 beta-dihomoprostaglandins and can compete with endogenous arachidonic acid for conversion by cyclooxygenase. These findings suggest that adrenic acid may reduce the formation of prostaglandin I2 by the blood vessel.