Alveolar transfer and metabolism of eicosanoids in the rat

Alveolar transfer of eicosanoids was studied in the rat after instillation of [3H] prostaglandins, leukotrienes, and arachidonate into the distal airways. The percentage of originally added label remaining in lung or lavage was determined 2 min after instillation, with the remainder of the label having been transferred out of the lung. Peptidoleukotrienes were found to be largely (greater than 85%) retained in the lung after 2 min, and even after 15 min, more than 50% of the added radiolabel remained in the lung. In clear contrast, greater than 90% of the radiolabeled prostaglandin (PG) D2 was removed from the lung within 2 min after instillation. PGE2, thromboxane B2, leukotriene (LT) B4, and 5-hydroxyeicosatetraenoic acid (5-HETE) were also quickly removed from the lung, with less than 30% of the added label remaining in the lung after 2 min. Arachidonic acid and 6-keto-PGF1 alpha were removed more slowly from the lung, with 40 to 70% remaining in the lung 2 min after instillation. The arachidonic acid remaining in the lung was largely esterified into phospholipids, especially phosphatidylcholine. The 5-HETE radiolabel remaining in the lung was also associated in part with phosphatidylcholine. The radioactivity remaining in the lung after [3H] LTB4, 6-keto-PGF1 alpha, PGD2, and thromboxane B2 instillation reflected predominantly unmetabolized eicosanoids. The peptidoleukotrienes underwent a slow metabolism from LTC4 to LTD4 to LTE4. In addition, LTE4 was metabolized to a more polar product with chromatographic properties identical to those of N-acetyl LTE4. Rat lung slices and homogenates also metabolized peptidoleukotrienes via this pathway, although less N-acetyl LTE4 was produced.(ABSTRACT TRUNCATED AT 250 WORDS)