Role of Na Entry in the Regulation of Proliferation of Cultured Fibroblasts: Effect of Vasopressin

Abstract

This study reports the measurement of monovalent ion fluxes and content in cultured cells. The study is based on the fact that normal,untransformed fibroblasts reduce their rate of entry into the S (DNA synthesizing) phase of the cell cycle and accumulate in a viable quiescent state (Go/G1) when the content of growth factors in the medium becomes limiting. Addition of fresh serum or growth factors to such quiescent cells stimulates a complex array of biochemical events leading to DNA synthesis and cell division (1,2). Recently,a variety of information has led to the suggestion that the uptake of sodium plays an important role in the regulation of cell proliferation (3). Serum, the most widely used stimulator of cell proliferation, rapidly increases sodium entry into quiescent cells (4) and stimulates the sodium potassium pump (5). A variety of other growth factors including platelet derived growth factor (6) and fibroblast derived growth factor (7) also increase sodium entry and/or activity of the sodium potassium pump. The synthesis of DNA is dependent upon the concentration of sodium in the extracellular medium (4). The proliferative response to serum is strikingly inhibited by ouabain, an inhibitor of the sodium potassium pump (5), and by amiloride, an inhibitor of sodium entry into the cells (3). In certain transformed cells,the entry of sodium and the activity of the sodium potassium pump greatly exceeds that found in the nontransformed parent cells (3,6).