Hormones increase mRNA of cyclic-nucleotide-gated cation channels in airway epithelia.
Previous studies have shown that the mRNA of cyclic-nucleotide-gated nonselective cation (CNG) channels is expressed in rat airway epithelia and that these channels contribute to sodium-mediated short-circuit currents in cultured rat tracheal epithelia. Patch-clamp studies from human A549 cells indicate that these channels contribute to cGMP-stimulated L-cis-diltiazem- and dichlorobenzamil-inhibited whole-cell sodium currents. This study demonstrates that mRNA for primary and secondary subunits of CNG channels, halphaCNG1 and hbetaCNG1 respectively, are expressed in several human airway cell lines, including normal and cystic fibrosis bronchial airway cells, in normal and cystic fibrosis tracheal airway cell lines and nasal polyp tissue from a cystic fibrosis patient. The mRNA of ralphaCNG1 in rat lung increased in response to increased circulating glucocorticoids and decreased in animals with lowered circulating glucocorticoids after aminoglutethimide treatment. Likewise the mRNA of halphaCNG1 increased in the presence of glucocorticoids in cultured alveolar airway cells. The mRNA of alphaCNG1 in rat lung was also increased in response to a low-salt diet and lowered in animals fed a high-salt diet. Likewise the mRNA of alphaCNG1 was increased in response to increased aldosterone and decreased in animals given spironolactone. These results suggest that mRNA for alphaCNG1 increases in response to elevated glucocorticoids or mineralocorticoids. Because alphaCNG1 is a functional sodium entry channel in both rat and human airway epithelial cells, if channel protein is also elevated this channel could mediate an increase in sodium absorption across lung epithelia in response to circulating hormones.
Qiu
W
W
Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Laheri
A
A
Leung
S
S
Guggino
S E
SE
D000818:Animals; D001980:Bronchi / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D054815:Cyclic Nucleotide-Gated Cation Channels; D003550:Cystic Fibrosis; D004039:Diet, Sodium-Restricted; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008168:Lung / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012137:Respiratory System / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013539:Simian virus 40; D013148:Spironolactone / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism
D054815:Cyclic Nucleotide-Gated Cation Channels; D005938:Glucocorticoids; D007473:Ion Channels; D012333:RNA, Messenger; D013148:Spironolactone