Evaluation of [iodine-125]N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3- propanediamine lung uptake using an isolated-perfused lung model

Lung uptake of N,N,N'-trimethyl-N'-[2-Hydroxy-3-methyl-5-iodobenzyl]-1,3- propanediamine (HIPDM) has been reported, but the mechanism of this process has not yet been established. Thus, single-pass [125I]HIPDM accumulation was studied in rat lungs perfused with a Krebs-Ringer bicarbonate buffer containing 4.5% bovine albumin. Iodine-125 HIPDM lung accumulation was monitored by the percent of extraction per gram of lung tissue. Iodine-125 HIPDM lung uptake did not appear to occur by simple diffusion. As the time of perfusion was increased from 2 to 15 min, the rate of uptake of 2 microM [125I]HIPDM decreased by 40%. During a 2-min perfusion, 98.6% +/- 6.7 (n = 8) extraction was observed with 2 microM [125I]HIPDM, but only 38% +/- 2.0 (n = 3) was extracted when the [125I]HIPDM concentration was 1 mM. The addition of 1 mM chlorpromazine, propranolol or imipramine also decreased [125I]HIPDM lung uptake to 43.0% +/- 1.5, 51.4% +/- 2.2, and 49.8% +/- 0.8, respectively, (each n = 4 - 6, p less than 0.001). Cold (4 degrees C) had little effect on pulmonary accumulation (77.7% +/- 7.4, n = 5, p less than 0.01), and the addition of ouabain or the use of sodium-free medium had no effect. Thus, pulmonary [125I]HIPDM accumulation does not appear to occur by sodium-dependent active transport. Rather, its uptake appears to be similar to the uptake of other basic amines, such as propranolol and imipramine, which are known to bind by physico-chemical interactions to pulmonary endothelial cell membranes and reflect pulmonary vascular surface area