EFFECTS OF SALMETEROL (S) ON PHOSPHATIDYLCHOLINE (PC) SECRETION BY TYPE II CELLS. 2007

β adrenergic agents enhance secretion of PC by adult and fetal type II cells (T_IIC). S is a highly selective, long acting β₂ adrenergic agonist which binds to an exosite domain of the β₂ receptor. We studied the effects of S on PC secretion by adult T_IIC cultures which were incubated for 20-22 hours with³ H-Choline(2μc/ml) and placed in fresh media. To study dose-response, cultures were exposed to 1, 10, 50 & 100nM S for 90 minutes(min). In blocking studies, cultures were exposed to 10μM propranolol (P) for 30min & then to 50nM S for 90min. To determine time course of S effects, cells were incubated with 50nM S for 90min & then placed in fresh media for 180, 360 & 720min. Media & cells were separated & lipids extracted. PC was isolated by thin-layer chromatography and radioactivity determined. PC secretion=(cpm in media/cpm in cells + media) X 100. Stimulation = (Treated/Control secretion)X100. Release of Lactic dehydrogenase, a measure of cellular disruption, was <5%. Data are expressed as M ± SE (n=5, in duplicate):Table

Table 1

S stimulates PC secretion in a concentration dependent manner. The maximum effective concentration=50nM. EC₅₀, 50% of maximal stimulation=25nM. Inhibition by P confirms that S effects is mediated by β₂ receptors. OT₅₀, the time to achieve 50% of maximal effect=45min. RT₅₀, the time to achieve 50% recovery from maximal effect=185min. S has a longer duration of action, greater than 6 hours, when compared to otherβ agonists. This is the first study to demonstrate the effects of S on PC secretion by T_IIC.