The perfused rat lung as a model for studies on the formation of surfactant and the effect of Ambroxol on this process

Autor: Post, M., Batenburg, J. J., Schuurmans, E. A. J. M., Oldenborg, V., van der Molen, A. J., van Golde, L. M. G.
Zdroj: Lung; December 1983, Vol. 161 Issue: 1 p349-359, 11p
Abstrakt: The isolated perfused rat lung was used as a model to investigate the synthesis of surfactant phospholipids from various radioactive precursors and the effect of Ambroxol, a bronchial secretolyticum, on this process. Lungs were ventilated and perfused for periods up to 5 h without detectable development of pulmonary edema. The lungs remained metabolically stable during the entire period of perfusion. Both in whole lung tissue and in the surfactant fraction the radioactive substrates incorporated predominantly into phosphatidylcholine and phosphatidylglycerol. The degree of saturation of labelled phosphatidylcholines synthesized during perfusion with [Me-14C]choline, D [U-14C]glucose, [1(3)-3H]glycerol and [1-14C]palmitate was higher in surfactant than in whole lung tissue. A delayed incorporation into surfactant phospholipids was observed for all precursors. Under the conditions employed, glucose carbon was recovered mainly in the glycerol backbone of phosphatidylcholine and phosphatidylglycerol. Compared to glucose, glycerol appeared to be a minor substrate for lung lipid formation. If the lungs were perfused after pretreatment of the rats with Ambroxol on three consecutive days, the incorporation of labelled choline and glycerol into pulmonary phospholipids was found to be enhanced. This stimulation was more pronounced in the surfactant fraction than in whole lung tissue. The stimulatory effect on the formation of surfactant lipids was smaller after pretreatment of the animals with Ambroxol for one day. The results of the present study suggest that Ambroxol may specifically stimulate the synthesis of phospholipids in the alveolar type II cells and that the drug may not only affect the formation but also the secretion of surfactant lipids by these cells.
Databáze: Supplemental Index