Regulation of transport across pulmonary alveolar epithelial cell monolayers.
Domes are formed in large numbers by primary cultured monolayers of type II alveolar epithelial cells from rat lungs. These fluid-filled structures are formed by active transport of solute from medium to substratum, with water following passively. In the present study, we used dome-forming monolayers to study the regulation of alveolar epithelial transport processes by determining the effects on dome formation of adenosine 3',5'-cyclic monophosphate (cAMP) analogues, phosphodiesterase inhibitors, neurotransmitters, and vasopressin (antidiuretic hormone, ADH). The cAMP analogues (dibutyryl cAMP and 8-bromo-cAMP) and phosphodiesterase inhibitors (theophylline, papaverine, and isobutylmethylxanthine) caused large increases in dome formation by 24 h. ADH and beta-adrenergic agonists (epinephrine, terbutaline, and isoproterenol) also caused significant increases in dome density. The beta-agonist response was completely eliminated in the presence of the beta-blocker propranolol. Dibutyryl guanosine 3',5'-cyclic monophosphate and acetylcholine (cholinergic agonist) had no effect on dome formation, whereas the alpha-adrenergic agonist methoxamine caused a small but significant decrease in dome formation. These findings suggest that the active solute flux resulting in dome formation by type II alveolar epithelial cell monolayers is increased by substances expected to elevate intracellular cAMP (or analogue) concentrations. An attractive speculation having major implications for lung fluid balance is that transepithelial fluxes can be modulated by endogenous, and perhaps exogenous, chemical agents in adult mammalian alveolar epithelium in vivo.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003470:Culture Media; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004847:Epithelial Cells; D008854:Microscopy, Electron; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology; D014882:Water-Electrolyte Balance
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D003470:Culture Media; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D014667:Vasopressins; D000242:Cyclic AMP