Abstract
A procedure for the dispersal of rat lung into individual cells has been described. Further fractionation of these cells yielded populations enriched in Type II alveolar epithelial cells. These preparations maintained the ability to consume oxygen and oxidise glucose but progressively lost the ability to accumulate paraquat and putrescine. It is suggested that lung cells, isolated by these methods, are not suitable for the quantitative study of specific functional activities. The accumulation of both paraquat and putrescine, into rat lung slices, has been compared in animals from different sources and after perfusion or lavage. It is proposed that both compounds are accumulated by a common uptake system. The accumulation of putrescine into rat lung slices has been observed to obey saturation kinetics (apparent Km = 11.5 muM, V[max] = 331 nmol/g wet wt lung/hr) for low substrate concentrations (< 100 muM). Structure-activity studies, to characterise the requirements for inhibition of putrescine accumulation into rat lung slices, have indicated that inhibitors should possess 1, and preferably 2, cationic sites separated by a distance of at least 4 carbon atoms. The most potent inhibitors found were agmatine and the anti-leukaemic drug, methylglyoxal bis (guanylhydrazone), (methyl GAG). Diamines which had an alpha-carboxylic acid (e.g. ornithine) were not effective inhibitors. The potential of methyl GAG to reduce paraquat toxicity in vivo has also been investigated. The accumulation of paraquat and the endogenous polyamines into human lung slices, by a common uptake system, has also been demonstrated. Putrescine accumulation also obeys saturation kinetics in man (apparent Km = 2-11muM, V[max]= 99-249 nmol/g/hr), at low substrate concentrations (< 1 mM). This system appears very similar to that in the rat lung. The accumulation system described appears different to those responsible for monoamine uptake in the lung, or amino acid uptake in other tissues. However, apparently similar polyamine uptake systems have been described in a number of tissues including brain.