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Diamine uptake by rat lung type II cells in vitro
V I Oreffo1, R A John, R J Richards
1Department of Biochemistry, University of Wales, College of Cardiff, U.K.
Biochemical Pharmacology
|April 15, 1991
Summary
Lung epithelial type II cells actively accumulate the diamine putrescine, a process crucial for cell proliferation. The herbicide paraquat partially inhibits this uptake, suggesting distinct but overlapping transport mechanisms.
Area of Science:
- Cell Biology
- Toxicology
- Pulmonary Medicine
Background:
- Lung epithelial type II cells produce pulmonary surfactant.
- Type II cells proliferate following alveolar injury.
- Amine accumulation, particularly putrescine, is linked to type II cell proliferation.
Purpose of the Study:
- To investigate the active accumulation of putrescine by alveolar type II cells.
- To determine if the herbicide paraquat shares the putrescine uptake system.
- To characterize the interaction between paraquat and putrescine transport.
Main Methods:
- Isolation and culture of alveolar type II cells.
- Measurement of putrescine uptake kinetics (Km, Vmax).
- Assessment of paraquat's inhibitory effects on putrescine accumulation.
Main Results:
- Putrescine uptake is an energy-dependent process obeying saturation kinetics.
- Paraquat acts as a partially competitive inhibitor of putrescine accumulation.
- Paraquat Ki (69 microM) aligns with predicted Km (70 microM) from lung slice studies, indicating distinct binding sites.
Conclusions:
- Alveolar type II cells possess a specific, saturable uptake system for putrescine.
- Paraquat interacts with this system but does not fully displace putrescine, suggesting shared but not identical transport sites.
- This interaction provides insights into the mechanism of paraquat toxicity in lung cells.