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Active uptake of propranolol by isolated rabbit alveolar macrophages and its inhibition by other basic amines
Abstract:
Propranolol and other basic amines are concentrated by the lung. To test the possibility that the alveolar macrophage might participate in this process, the uptake of dl-[3H]propranolol was studied in macrophages isolated from healthy male rabbits. Uptake was time, temperature, and pH dependent and was reduced in the presence of inhibitors of cellular energy metabolism, such as sodium azide, iodoacetate, sodium cyanide and 2,4-dinitrophenol. It was abolished by sonication of the cell suspension. Scatchard plots suggested at least three uptake processes, one of which appeared to be partition. Uptake of dl-[3H]propranolol was inhibited equally by increasing concentrations of both the dextro- and the levo-isomers, as well as the racemate. It was also markedly inhibited by the lysomotropic agents, ammonium chloride and chloroquine, and by a number of tertiary amines including imipramine, chlorpromazine and methadone. Endogenous amines, including noreprinephrine, epinephrine and histamine had no effect on uptake. These observations suggest that uptake processes in the lung for exogenous basic amines may differ from those for endogenous amines. Although uptake of endogenous amines has been localized to the vascular endothelium, the lysosome may be one intracellular site of accumulation for exogenous amines.
Insights
Alveolar macrophages concentrate propranolol, a basic amine, via energy-dependent processes. This lung uptake mechanism for exogenous amines may differ from endogenous amine uptake.
Area of Science:
- Pharmacology
- Cell Biology
- Pulmonary Medicine
Background:
- The lung concentrates propranolol and other basic amines.
- The role of alveolar macrophages in this concentration process is not fully understood.
Purpose of the Study:
- To investigate the uptake of dl-[3H]propranolol by rabbit alveolar macrophages.
- To determine if alveolar macrophages contribute to lung amine concentration.
Main Methods:
- Isolated alveolar macrophages from healthy male rabbits.
- Studied dl-[3H]propranolol uptake under various conditions (time, temperature, pH, energy metabolism inhibitors).
- Utilized Scatchard analysis and tested inhibition by isomers, tertiary amines, and lysomotropic agents.
Main Results:
- Propranolol uptake was time, temperature, and pH-dependent.
- Uptake was reduced by cellular energy metabolism inhibitors and abolished by sonication.
- Scatchard plots indicated at least three uptake processes, including partition.
- Uptake was inhibited by isomers, tertiary amines, and lysomotropic agents but not by endogenous amines.
Conclusions:
- Alveolar macrophages actively take up exogenous basic amines like propranolol through energy-dependent mechanisms.
- Lysosomes may be intracellular sites for exogenous amine accumulation in macrophages.
- Lung uptake mechanisms for exogenous and endogenous amines likely differ.