Prostaglandin E1 uptake by isolated cat lungs perfused with physiological salt solution

Abstract

The instantaneous extraction of prostaglandin E1 (PGE1) was measured after a bolus injection of PGE1 and [14C]dextran in to the pulmonary artery of isolated cat lungs perfused with a physiological salt solution [Krebs-Ringer-bicarbonate buffer (KRB)]. The extraction ratio vs. time curves exhibited characteristic shapes. For low injected doses of PGE1, the extraction ratios were constant early in time, whereas for high doses, they were concave upward. To evaluate the data, we used a model assuming homogeneous perfusion and a saturable uptake mechanism (Michaelis-Menten kinetics) for the PGE1. The model was used in a linear regression analysis to estimate Vmax and Km. The kinetic parameters were compared with our previous results for blood-perfused lungs, and it was found that the values of Km were significantly smaller than in blood-perfused lungs but that the values of Vmax were not significantly different. These results were consistent with the observation that PGE1 uptake was greater in KRB- than in blood-perfused lungs when the dose of PGE1 was low but that the difference disappeared at high doses. The absence of plasma protein binding in KRB-perfused lungs may be responsible for the lower Km.