Stimulation of lung surfactant secretion by endothelin-1 from rat alveolar type II cells.
Endothelin-1 (ET-1), a potent vasoactive peptide released by endothelial cells, alters cytosolic Ca2+ and phosphoinositide metabolism in cells of myogenic and nonmyogenic origin. We evaluated the effect of ET-1 on surfactant phosphatidylcholine (PC) secretion from alveolar type II cells labeled with [methyl-3H]choline. ET-1 stimulated the secretion of PC in a time- and dose-dependent manner. Binding of 125I-labeled ET-1 to type II cell membranes was saturable at approximately 1 nM and suggested the presence of a single type of receptor. The secretagogue effect of ET-1 was independently inhibited by nifedipine and nitrendipine, both L-type calcium channel blockers, and removal of extracellular calcium. ET-1 also increased cellular diacylglycerol content by approximately 50% within 30 s, which could not be attenuated by pretreatment with nifedipine, suggesting an early activation of protein kinase C that was independent of Ca2+ influx. Further, ET-1-stimulated PC secretion was also blocked by inhibitors of protein kinase C. Collectively, these results indicate that the binding of ET-1 to type II cells is coupled to the activation of protein kinase C, which increases calcium influx through L-type calcium channels, and results in increased secretion of lung surfactant. Since ET-1 is released from pulmonary micro- and macrovasculature endothelial cells in close proximity to type II cells, our findings support the novel concept that endothelial cells interact with alveolar type II cells in a paracrine fashion to regulate surfactant secretion.
Sen
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Institute for Environmental Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Grunstein
M M
MM
Chander
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A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D009543:Nifedipine; D002118:Calcium