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  • Title: Chlorphentermine uptake by rabbit lung slices.
    Author: Angevine LS, Mehendale HM.
    Journal: Toxicology; 1980; 16(2):139-52. PubMed ID: 7414614.
    Abstract:
    Slices of rabbit lung tissue (approximately 150 mg; 0.5 mm) were incubated in 5 ml of Krebs-Ringer phosphate buffer, in the presence of 0.25 mM [14C]chlorphentermine (CP) with shaking at 37 degrees C and under an atmosphere of an O2/CO2 mixture (95 : 5). Incubation medium (M) and tissue (T) were analyzed for radioactivity. Uptake of CP reached a plateau after 30 min at a T/M ratio of 20. Upon varying the concentration of [14C]CP from 0.125 mM to 2 mM, the concentration-response curve was seen to saturate and the T/M ratio decreased with increasing concentration. Substituting LiCl for NaCl or increasing the K+ content in the medium decreased CP uptake. Incubation of slices with Na+-pump inhibitors, harmaline and iodoacetate, significantly decreased CP uptake. Chloroamphetamine, desimipramine, imipramine, morphine, chlorpromazine, dieldrin, methadone, amphetamine (each at 1 mM) and incubation at 10 degrees C inhibited CP uptake. Imipramine and amphetamine were both effective in displacing previously accumulated CP from the tissue slices. Efflux of CP from the lung slices was biphasic and was not affected by removal of Na+ from the medium. Binding of CP to lung homogenate was unaffected by substituting LiCl for NaCl or by the presence of 1 mM iodoacetate. However, 1 mM harmaline or 1 mM imipramine decreased CP binding. These studies offer evidence for a partially Na+-dependent, active uptake process for pulmonary sequestration of CP compatible with earlier findings obtained with perfused intact lung preparations.
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