EFFECT OF CHLORPHENTERMINE PRETREATMENT ON CHLORPHENTERMINE UPTAKE BY ISOLATED PERFUSED RAT LUNG

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (1) , 68-73
Abstract
Chlorphentermine (CP), an anorectic agent currently in use in humans, is known to be highly accumulated in the lung, causes pulmonary phospholipidosis, and has been suspected of causing pulmonary hypertension. These studies were undertaken to characterize the uptake and accumulation processes and to examine the effect of subacute CP treatment on the uptake kinetics of CP in the rat lung. Animals were treated orally with a saline solution of CP (50 mg/kg per day) for 7 days, and the controls received the vehicle only. Artificially ventilated, isolated rat lung preparations were perfused with Krebs-Ringer bicarbonate buffer containing bovine serum albumin. CP was not metabolized by control or pretreated perfused lungs or by their 9000 g supernatant or microsomal fractions. In recirculating perfusion experiments, steady-state uptake was reached after 20 min of perfusion with 0.17 mM CP. Lungs from rats treated with CP as described above accumulated CP to a greater extent and more rapidly than did lungs from control rats. Lungs from rats treated with CP accumulated greater quantities of CP than control lungs during single-pass perfusion experiments. Whereas control lungs reached a steady state uptake within 7 min, lungs from CP-treated animals failed to reach a steady-state uptake during the 10-min perfusion. The lungs from CP-treated rats retained most of the accumulated CP and exhibited a significantly increased half-life of efflux in comparison to control rats. Removal of Na+ from the perfusion medium or the addition of harmaline decreased the half-life of CP uptake and the amount of CP accumulated by the lung.