Metabolism of [2-14C]prostaglandin E1 on passage through the pulmonary circulation

A multiple indicator dilution technique was used to study inactivation of [14C]prostaglandin E1 (PGE1) by isolated cat lungs. A bolus containing [2-14C]PGE1, indocyanine green dye and 3HOH was rapidly introduced into the blood entering the pulmonary artery. Sequential samples of the venous effluent were collected and analyzed for 3H, dye, and 14C. The 14C-labelled compounds were separated by thin-layer chromatography, and the quantity of PGE1 and its metabolites contained in each sample was determined (radiochromatogram scanning). Recovery of the dye and 3H was complete within the sampling period. However, only 79% of the injected 14C emerged from the lung within this period, 36% as [14C]PGE1, and 43% as two less polar metabolites. The mean transit times (including connecting tubing) for the unmetabolized [14C]PGE1 and the dye were 9.1 and 8.7 s, respectively. The apparent mean transit times for 14C in the metabolites were considerably longer, 12.4 and 14.3 s. The 3HOH mean transit time was 10.7 s. These data are compatible with an extraluminal site for PGE1 metabolism.