DIAMINE UPTAKE BY RAT LUNG TYPE-II CELLS-INVITRO

Lung epithelial type II cells are responsible for synthesising and secreting pulmonary surfactant which reduces surface tension and prevents lung collapse. Type II cells replace type I cells and can proliferate in response to alveolar injury. An important aspect of this proliferation may be the ability of type II cells to accumulate amines actively, particularly the endogenous diamine putrescine. Putrescine is accumulated into isolated alveolar type II cells by an energy-dependent process. The uptake obeys saturation kinetics for which an apparent K(m) of 14.7-mu-M and V(max) of 130 pmol/mu-g DNA/hr was derived. The inhibitory effects of structurally similar amines on putrescine accumulation are described. As the herbicide paraquat has been suggested to share the same uptake system as putrescine from lung slice studies, this phenomenon was investigated in type II cell cultures. The results demonstrated that paraquat is a partially competitive inhibitor of putrescine accumulation in the cells. The K(i) for the inhibition of putrescine uptake by paraquat in type II cells was calculated to be 69-mu-M, a value which closely matches the K(m) for paraquat (70-mu-M) predicted from lung slice studies. In molecular terms, the partial nature of the competition indicates that paraquat and putrescine do not occupy identical sites. Saturation of its site by paraquat reduced the affinity of putrescine 3.6-fold, but did not abolish it.