MITOCHONDRIA ACT AS A RESERVOIR FOR THE BASIC AMINE HIPDM IN THE LUNG

The lungs are a site for the uptake, accumulation, and storage of exog enous basic amines. The compound trimethyl-N'-(2-hydroxy-3-methyl-5-io dobenzyl)-1,3 propanediamine (HIPDM) is a basic amine that can be labe lled with radioactive iodine and detected by external counting, Intrav enously injected I-123-HIPDM is extracted by the human lung, where it is retained in a slowly effuxable pool. In the present study, we measu red HIPDM lung kinetics and subcellular distribution in rabbits given i.v. I-125-HIPDM. Rabbits were killed from 2 min to 5 h after injectio n, and the radioactivity retained in their lungs was measured, Subcell ular lung fractions (nuclear, mitochondrial, lysosomal, microsomal, an d postmicrosomal supernatant) were assayed for HIPDM radioactivity, pr otein contene, and distribution of specific marker enzymes. HIPDM lung clearance in rabbits was nearly identical to that of humans, Virtuall y all the HIPDM radioactivity in lungs (98+1%) was associated with sub cellular membranous structures. The highest HIPDM specific radioactivi ty was found in the mitochondrial Fraction, and the subcellular distri bution profile closely resembled that of the mitochondrial marker enzy me succinate cytochrome c reductase, No redistribution of HIPDM among subcellular compartments was observed over a 5 h period after injectio n. The data indicate that mitochondria act as reservoir for HIPDM in t he lungs and contribute to the pulmonary persistence of this compound, HIPDM can be used to investigate the pulmonary uptake of basic amines in health and in lung disease.