Effects of salmeterol on secretion of phosphatidylcholine by alveolar type II cells.
Beta-adrenergic agents enhance secretion of phosphatidylcholine (PC) by adult and fetal type II cells. We have previously shown that terbutaline stimulates secretion of PC by fetal type II cells, but the response wanes after 30 minutes. We studied the effects of salmeterol, a highly selective, long-acting beta2-adrenergic agonist that does not cause receptor desensitization, on PC secretion by adult type II alveolar cells in primary culture. Release of lactate-dehydrogenase was < 4% and did not vary with the concentration of salmeterol. Salmeterol stimulated PC secretion in a concentration-dependent manner. The maximum effective-concentration tested was 50 nM and the EC50 was 11.40 +/- 1.14 nM. Propranolol inhibited the effect of salmeterol on release of PC, confirming that the effects of salmeterol are mediated by beta-receptors. OT50, the time for onset of action, was 32.0 +/- 1.6 minutes. RT50, the time to achieve 50% recovery from maximal stimulation was, 393.0 +/- 20.2 minutes. We conclude that salmeterol stimulates PC secretion by type II cells through activation of beta-adrenergic receptors and has a longer duration of action (>6 hours) compared to other beta2-agonists. Salmeterol may be a useful drug with which to study the role of receptor desensitization in the developmental changes in PC secretion.
Department of Pediatrics, University of Connecticut School of Medicine, Farmington 06030-2948, USA.
V H
VH
Kumar
C
C
Christian
M J
MJ
Kresch
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068299:Salmeterol Xinafoate
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D010713:Phosphatidylcholines; D000068299:Salmeterol Xinafoate; D011433:Propranolol; D007770:L-Lactate Dehydrogenase; D000420:Albuterol