Tyrosine kinase regulates epithelial sodium transport in A6 cells.
Insulin increases epithelial Na+ reabsorption, and many of its actions involve tyrosine kinase. We used tyrosine kinase inhibitors to examine the role of tyrosine kinase in the action of insulin. Pretreatment of Na+ transporting cells with tyrosine kinase inhibitors attenuates the subsequent action of insulin, suggesting that the action of insulin on epithelial Na+ transport involves tyrosine kinase activity. In addition to their effect on insulin-induced Na+ transport, the tyrosine kinase inhibitors also significantly reduce Na+ transport in Na(+)-transporting epithelial cells, suggesting that there is a significant tonic tyrosine kinase activity that modulates epithelial Na+ transport. Using patch-clamp methods, we found that one inhibitor, genistein, reduces the number of active Na+ channels in cell-attached patches without significantly affecting the open probability of any remaining channels. The effects of the tyrosine kinase inhibitors are not due to inhibition of protein kinase A (PKA), since H89, a PKA inhibitor, does not affect Na+ transport of control cells (as the tyrosine kinase inhibitors do), and the tyrosine kinase inhibitor, genistein or tyrphostin 23, does not alter the stimulation of ion transport by 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, a membrane-permeable adenosine 3',5'-cyclic monophosphate analogue (as H89 does).
Matsumoto
P S
PS
Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322.
Ohara
A
A
Duchatelle
P
P
Eaton
D C
DC
D000818:Animals; D001692:Biological Transport; D002396:Catechols / Q000494:pharmacology; D002460:Cell Line; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D019833:Genistein; D007328:Insulin / Q000502:physiology; D007529:Isoflavones / Q000494:pharmacology; D009399:Nephrons / Q000166:cytology / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D020032:Tyrphostins; D014982:Xenopus laevis
D002396:Catechols; D007328:Insulin; D007529:Isoflavones; D009570:Nitriles; D010636:Phenols; D020032:Tyrphostins; C062898:lavendustin A; D012964:Sodium; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C060641:tyrphostin A23