It was shown that activation of the Na+/H+ antiporter resulting in an increase of intracellular pH (pH,) by 0.24.3 is a necessary stage of cell stimulation by soluble growth factors. Solid substrate can also be formally regarded as a growth factor since adhesion stimulates proliferation of various cell types. In the present study we have found that the attachment of mouse embryo fibroblasts to solid substrate is followed by an increase of pH, by approx. 0.3 units. pH shift occurs after the cell attaches to the substrate and is obligatory for cell spreading. The evidence for Na+/H+ antiporter involvement in the increase of pH, in substrate-attached cells is presented. It is suggested that signals for cell proliferation by chemical (soluble ligands) and physical (solid substrate) growth factors are transmitted similarly.Na+/H+ antiporter; Cell adhesion: Amiloride derivative

In Ehrlich ascites carcinoma cells, acidification of the cytoplasm down to pH 6.2–6.3 arrests DNA synthesis. Such acidification can be obtained by decreasing the pH outside the cell or, alternatively, by addition of a micromolar concentration of the K+/H+ antiporter nigericin. Thus, nigericin may be regarded as a new type of cytostatic, the effect of which is mediated by alteration of the intracellular pH.