Inhibition of phosphatidylcholine secretion by stilbene disulfonates in alveolar type II cells.
Various agents stimulate the secretion of lung surfactant from alveolar type II cells by increasing intracellular Ca2+, cyclic adenosine-3':5'-monophosphate (cAMP), or diacylglycerol. A few agents, including the purified surfactant protein A, are known to inhibit the secretion by an unknown mechanism. In the present study, we demonstrated that stilbene disulfonic acids, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), are potent but reversible inhibitors of lung surfactant secretion. The inhibition was concentration dependent, and the EC50 was 5 microM for DIDS and 50 microM for SITS. The inhibition was not specific to agonists for any one type of receptor, and was also observed for secretion stimulated by 8-bromo-cAMP, or tetradecanoyl phorbol acetate, suggesting that the site of inhibition was distal to the generation of intracellular second messengers. This was also supported by the failure of DIDS to block the stimulus-mediated increase in diacylglycerol content of type II cells. Further, DIDS and SITS were also inhibitory for basal secretion. Based on the reversibility of inhibition and the fact that inhibition was observed with both basal and stimulated secretion, we suggest that stilbene disulfonic acids affect a component of the exocytosis process that occurs at or near the plasma membrane.
Institute for Environmental Medicine, University of Pennsylvania, School of Medicine, Philadelphia 19104.
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000032:analysis; D015536:Down-Regulation; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D010713:Phosphatidylcholines / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013726:Terbutaline / Q000037:antagonists & inhibitors; D007507:Therapeutic Irrigation
D004075:Diglycerides; D010713:Phosphatidylcholines; D015221:Potassium Channels; D011663:Pulmonary Surfactants; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000255:Adenosine Triphosphate; D013726:Terbutaline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid