Metabolism of [2-14C]Prostaglandin E1 on Passage Through the Pulmonary Circulation

Abstract

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 PGE, 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.