Forskolin activation of apical Cl- channel and Na+/K+/2Cl- cotransporter via a PTK-dependent pathway in renal epithelium.
Forskolin induced the transepithelial Cl- transport (secretion) by activating the apical Cl- channel and basolateral Na+/K+/2Cl- cotransporter in renal epithelial A6 cells via an increase in cytosolic cAMP concentration. The cAMP activation of apical Cl- channel and Na+/K+/2Cl- cotransporter was partially mediated through a protein kinase A (PKA)-dependent pathway, but a PKA-independent pathway was also suggested to be involved in the cAMP activation. Therefore, we assessed a possibility of involvement of protein tyrosine kinase (PTK)-dependent pathway as a PKA-independent pathway in the cAMP activation by applying a PTK inhibitor, tyrphostin A23 (AG18). Tyrphostin A23 abolished the forskolin-induced transepithelial Cl- secretion by partially diminishing the activity of the Cl- channel and completely inhibiting the Na+/K+/2Cl- cotransporter. Further, forskolin increased phosphorylation of protein tyrosine, suggesting that cAMP activates PTK. These observations suggest that cAMP activates the Cl- channel and the Na+/K+/2Cl- cotransporter by activating PTK.
Niisato
N
N
Department of Cellular and Molecular Physiology, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan.
Marunaka
Y
Y
D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D016764:Cell Polarity; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009579:Nitrobenzoates / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D028021:Sodium-Potassium-Chloride Symporters; D020032:Tyrphostins / Q000494:pharmacology
D002352:Carrier Proteins; D018118:Chloride Channels; D002712:Chlorides; D009579:Nitrobenzoates; D028021:Sodium-Potassium-Chloride Symporters; D020032:Tyrphostins; D002034:Bumetanide; D005576:Colforsin; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D010042:Ouabain; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C060641:tyrphostin A23