Characterization and comparison of the role of beta-agonists on in vivo and in vitro surfactant-related phospholipid synthesis and secretion by fetal rabbit lung and isolated type II alveolar cells.
The role of beta-adrenergic stimulation in surfactant synthesis and secretion was investigated in the fetal lung. Fetuses were treated with isoxsuprine or saline on gestational day 24 by ip injection. Three days later the fetal lungs were lavaged and intracellular surfactant was isolated on a sucrose gradient. Concurrently undifferentiated type II alveolar cells were isolated from 24-day fetal rabbit lung and grown in vitro. In the in vivo portion of the study, examination of surfactant pool sizes revealed that only saline treatment produced a significant elevation in tissue-stored or secreted surfactant compared to untreated controls. Isoxsuprine appeared to inhibit the saline-induced increase. In the case of the intracellular surfactant, the phosphatidylcholine content per gram of lung was significantly increased after saline treatment. In vitro response of isolated type II alveolar cells to isoxsuprine was dependent on prior incubation of the cells for 24 h with conditioned medium. Isoxsuprine stimulated a dose-dependent decrease in the intracellular stores of radioactively labeled DSPC after 24 h of exposure to the drug. A corresponding increase in labeled DSPC in the culture medium was observed. Forth-eight hours after exposure to the drug, those cells that had secreted the highest level of DSPC displayed the highest levels of renewed synthesis of DSPC. This study indicates that the immature fetal lung can be induced to synthesize surfactant-related phospholipid by the stress of laparotomy and/or drug administration. Short-term exposure to beta-agonists is insufficient to stimulate secretion of surfactant stores. In contrast, isolated type II alveolar cells exposed to isoxsuprine respond by secreting DSPC.
Rasmusson
M G
MG
Department of Anatomy, Dalhousie University, Halifax, Nova Scotia, Canada.
Scott
J E
JE
Oulton
M R
MR
Temple
S
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D005333:Fetus / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D007556:Isoxsuprine / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000502:physiology*; D011817:Rabbits
D000318:Adrenergic beta-Agonists; D010743:Phospholipids; D011663:Pulmonary Surfactants; D007556:Isoxsuprine