title: Physiological effect of protein kinase C on ENaC-mediated lung liquid regulation in the adult rat lung.
abstract: Tight control of lung liquid (LL) regulation is vital for pulmonary function. The aim of this work was to determine whether PKC activation is involved in the physiological regulation of LL volume in a whole lung preparation. Rat lungs were perfused with a modified Ringer solution, and the lumen was filled with the same solution without glucose. LL volume was measured during a control period and after modulating drugs were administered, and net LL transepithelial movement (J(v)) was calculated. When the PKC activator PMA (10(-5) M) and the Ca(2+) ionophore ionomycin (10(-6) M) were instilled into the lung together, J(v) was significantly reduced (P = 0.03). This reduction was blocked by the PKC inhibitor chelerythrine chloride (10(-6) M; P = 0.56) and by a second PKC inhibitor GF109203X (10(-5) M; P = 0.98). When PMA and ionomycin were added with the β-adrenergic agonist terbutaline, the terbutaline-induced increase in J(v) was abolished. Addition of PMA and ionomycin with the epithelial Na(+) channel (ENaC) blocker amiloride had no additional inhibitory effect. Together, these results suggest that PKC is likely to be involved in LL absorption, and the ability of PMA/ionomycin to block the terbutaline-induced increase in J(v) suggests that the downstream target of PKC is ENaC.
authors.affiliation: Division of Biomedical Sciences, St. George's University of London, London, United Kingdom.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Soukup
authors.forename: Audra
authors.initials: A
authors.lastname: Benjamin
authors.forename: Maria
authors.initials: M
authors.lastname: Orogo-Wenn
authors.forename: Dafydd
authors.initials: D
authors.lastname: Walters
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077331:Ringer's Solution; D015398:Signal Transduction / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D053503:Epithelial Sodium Channels; D007211:Indoles; D007552:Isotonic Solutions; D008301:Maleimides; D026941:Sodium Channel Blockers; D015759:Ionomycin; C016658:phorbolol myristate acetate; D000584:Amiloride; D000077331:Ringer's Solution; C016299:chelerythrine; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013726:Terbutaline; D013755:Tetradecanoylphorbol Acetate