Using voltage-clamp technique, the role of tyrosine kinases and phosphatidylinositol kinases in the effect of oxidized glutathione (GSSG) and its pharmacological analogue, drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that preincubation of the skin with tyrosine kinase inhibitor genistein or with two structurally distinct phosphatidylinositol kinase inhibitors, wortmannin and LY294002, significantly decreased the stimulatory effect of GSSG or glutoxim on Na+ transport. The data suggest that GSSG and glutoxim might transactivate insulin receptor in the basolateral membrane of epithelial cells and trigger the signaling cascade, involving tyrosine kinases and phosphatidylinositol kinases, which lead to Na+ transport stimulation in frog skin.
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