Radiolabeled PGI2 was rapidly converted to 6,15-diketo-PGF1alpha by bovine mesenteric vessels, whereas 97% of 6-keto-PGF1alpha remained unmetabolized after 2 minutes of incubation.
Prostacyclin is rapidly metabolized to 6,15-diketo-PGF1alpha in blood vessels, indicating that measuring only its stable hydrolysis product 6-keto-PGF1alpha may underestimate PGI2 generation.
The activity of 15-hydroxyprostaglandin dehydrogenase has been shown to be high in both mesenteric arteries and veins; the present study suggests that it may be responsible for the inactivation of prostacyclin (PGI2). The cytoplasmic fractions of bovine mesenteric arteries and veins were incubated with radiolabeled PGI2 in the presence of NAD+ or NADP+. The substrate was rapidly converted to a product, which was isolated and identified as 6,15-diketo prostaglandin F1alpha, (6,15-diketo-PGF1alpha) by thin layer chromatography and gas chromatography-mass spectrometry. The initial reaction rate began to level off after less than 1 min of incubation at 37 degrees C. When radiolabeled 6-keto-PGF1alpha, the stable hydrolysis product of PGI2, was used as substrate under the same conditions, 97% was recovered unmetabolized after 2 min of incubation. Catabolism of PGI2 may be a major determinant of its levels in blood vessels and, therefore, may be of crucial importance to regulating the action of PGI2. Further, estimation of PGI2 generation by either tissues or organs may be misleading if only 6-keto-PGF1alpha is measured.
Wong et al. (Tue,) conducted a other in Prostacyclin metabolism. Radiolabeled PGI2 vs. Radiolabeled 6-keto-PGF1alpha was evaluated on Conversion to 6,15-diketo-PGF1alpha. Radiolabeled PGI2 was rapidly converted to 6,15-diketo-PGF1alpha by bovine mesenteric vessels, whereas 97% of 6-keto-PGF1alpha remained unmetabolized after 2 minutes of incubation.