Basic fibroblast growth factor stimulates surface expression and activity of Na+/H+ exchanger NHE3 via mechanism involving phosphatidylinositol 3-kinase

Na+/H+ exchanger NHE3 is a plasma membrane (PM) protein, which contributes to Na+ absorption in the intestine. Growth factors stimulate NHE3 via phosp hatidylinositol 3-kinase (PI3-K), but mechanism of this process is not clea r. To examine the hypothesis that growth factors stimulate NHE3 by modulati ng NHE3 recycling, and that PI3-K participates in this mechanism, we used P S120 fibroblasts expressing a fusion protein of NHE3 and green fluorescent protein. At steady state, similar to 25% of cellular NHE3 content was expre ssed at PM. Inhibition of PI3-K decreased PM expression of NHE3, which corr elated with retention of the exchanger in recycling endosomal compartment. In contrast, basic fibroblast growth factor (bFGF) increased PM expression of NHE3, which was associated with a S-fold increase in rate constant for e xit of the exchanger from the recycling compartment. Qualitatively similar effects of bFGF were observed in cells pretreated with PIS-K inhibitors, bu t their magnitude was only similar to 50% of that in intact cells. These da ta suggest that: (i) bFGF stimulates NHE3 by increasing PM expression of th e exchanger; (ii) PI3-K mediates PM expression of NHE3 in both basal and bF GF-stimulated conditions, and (iii) not all of the effects of bFGF on NHE3 expression are mediated by PI3-K, suggesting additional regulatory mechanis ms.