Kumar V H, Christian C, Kresch M J
Department of Pediatrics, University of Connecticut School of Medicine, Farmington 06030-2948, USA.
Life Sci. 2000 Mar;66(17):1639-46. doi: 10.1016/s0024-3205(00)00483-5.
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.
β-肾上腺素能药物可增强成年和胎儿Ⅱ型细胞中磷脂酰胆碱（PC）的分泌。我们之前已经表明，特布他林可刺激胎儿Ⅱ型细胞分泌PC，但30分钟后反应减弱。我们研究了沙美特罗（一种高度选择性、长效的β2-肾上腺素能激动剂，不会引起受体脱敏）对原代培养的成年Ⅱ型肺泡细胞PC分泌的影响。乳酸脱氢酶的释放量<4%，且不随沙美特罗浓度的变化而变化。沙美特罗以浓度依赖的方式刺激PC分泌。测试的最大有效浓度为50 nM，半数有效浓度（EC50）为11.40±1.14 nM。普萘洛尔抑制了沙美特罗对PC释放的作用，证实沙美特罗的作用是由β受体介导的。起效时间（OT50）为32.0±1.6分钟。从最大刺激恢复到50%的时间（RT50）为393.0±20.2分钟。我们得出结论，沙美特罗通过激活β-肾上腺素能受体刺激Ⅱ型细胞分泌PC，与其他β2-激动剂相比，其作用持续时间更长（>6小时）。沙美特罗可能是一种用于研究受体脱敏在PC分泌发育变化中作用的有用药物。
