Abstract
We previously reported the nongenomic mechanism of hypotonicity-induced renal Na+ reabsorption which involves protein tyrosine kinase (PTK) activation. However, it is still unknown what type of PTK mediates this stimulation. In the present study, we investigated the role of receptor-type tyrosine kinase (RTK) on the hypotonic stimulation of Na+ transport. In monolayers of A6 cells, a renal cell line derived from Xenopus laevis, we observed inhibitory effects of AG1478 (an inhibitor of EGF receptor) and AG1296 (an inhibitor of PDGF receptor) on both the hypotonicity-induced stimulation of Na+ transport and the hypotonicity-induced ligand-independent activation of EGFR. Next, we investigated a linkage between RTK and MAP kinase family members, indicating that ERK1/2 and JNK, but not p38 MAPK, are activated in the downstream of RTK and only JNK was involved in the hypotonic induction of Na+ transport. A further study suggests that RTK-JNK cascade contributes to the protein synthesis-independent early phase in the hypotonicity-induced Na+ absorption, but not to the protein synthesis-dependent late phase. Further, the present study suggests involvement of phosphatidylinositol 3-kinase in RTK-JNK cascade-mediated Na+ transport. These observations indicate that: 1) hypotonic stress activates JNK via RTK through a ligand-independent pathway, 2) the RTK-JNK cascade acts as a mediator of the hypotonic stress for stimulation of Na+ transport, and 3) PI3-kinase is involved in the RTK-JNK cascade to hypotonic stress-induced stimulation of Na+ transport. [J Physiol Sci. 2008;58 Suppl:S204]
