STIMULATION OF NET ACTIVE ION-TRANSPORT ACROSS ALVEOLAR TYPE-II CELL MONOLAYERS

The active transcellular transport of electrolytes across the alveolar epithelium probably plays an important role in alveolar fluid homeostatis by helping to maintain the alveolus relatively free of fluid. To better understand the factors regulating active ion transport across alveolar epithelial cells, we examined the effect of a number of pharmacologically active agents on the bioelectric properties of alveolar type II cells in primary culture. Alveolar type II cells were isolated from adult male rats and cultured on collagen-coated Millipore filters for 6-14 days. The bioelectric properties of these monolayers were determined in Ussing-type chambers. The addition of 10-3 M 8-bromoadenosine 3'',5''-cyclic monophosphate (8-BrcAMP) increased the short-circuit current (Isc) from 2.9 .+-. 0.75 to 6.9 .+-. 0.73 .mu.A/cm2 (means .+-. SE; n = 8) and decreased the transepithelial resistance. Cholera toxin, 3-isobutyl-1-methylxanthine, and terbutaline sulfate produced similar increases in Isc and decreases in resistance. The Isc stimulated by 8-BrcAMP was Na but not Cl dependent and could be blocked by amiloride but not by furosemide. Thus 8-BrcAMP and agents that increase intracellular cAMP can stimulate a Na-dependent net active ion transport across alveolar type II cell monslayers. Similar regulatory mechanisms may be involved in controlling solute and fluid movement across the alveolar epithelium in vivo.