Prostaglandin removal and metabolism by isolated perfused rat lung

Abstract

We have investigated the mechanism(s) involved in the removal of prostaglandins (PG) from the pulmonary circulation by the lung. Unidirectional fluxes of PG from the circulation into the lung are measured in an isolated perfused rat lung preparation. Evidence is presented which suggests that a transport system for PG exists in lung tissue. This transport system is responsible for the removal of some PG from the circulation by the lung. PGE1 and PGF2alpha are substrates for this system, whereas PGB1, PGA1, and 15-keto-PGF2alpha are not. Since PGA1 is a substrate for the intracellular PG dehydrogenase, the selectivity of the lung's metabolism system for circulating PG is probably due to the selectivity of the transport system for PG. It is shown that the percentage of the pulmonary arterial concentration (CA) of PGE1 or PGF2alpha that is metabolized on passage through the pulmonary circulation decreases rapidly as CA increases. When the lungs were perfused with PGE1(PGF2alpha), the metabolites detected in the venous effluent were 15-keto-PGE1 (PGF2alpha) and 15-keto-13, 14-dihydro-PGE1 (PGF2alpha). The time course pattern of the appearance of metabolites in the venous effluent after the initiation of a constant CA, and the relative concentrations of the metabolites in the venous effluent, were examined as a function of CA.