Beschreibung:
<jats:title>Abstract</jats:title><jats:p>The role of Na <jats:sup>+</jats:sup> transport systems in the mitogenic signal induced by growth factors was studied, and it was shown that two Na + transport systems contribute to the early increase in cytoplasmic Na + in response to serum growth factors, namely the amiloride‐sensitive Na<jats:sup>+</jats:sup>/H + antiport and the bumetanide‐sensitive Na + /K + /CI‐ cotransport. Bumetanide or amiloride, when added separately, inhibited part of the increase in cytoplasmic Na +, as a response to the addition of serum to quiescent BALB/c mouse 3T3 fibroblasts. Each drug also suppressed part of the stimulation of the ouabain‐sensitive Rb + influx, which was controlled by intracellular Na +. However, when both drugs were added together with serum growth factors, a complete inhibition of the early increase in [Na +], and subsequently a complete blockage of Na + /K + pump stimulation was obtained.</jats:p><jats:p>Amiloride or bumetanide, when added separately, only partially inhibited DNA synthesis induced by serum, 24% and 8% respectively. However, when both drugs were added together, at the time of serum addition to the quiescent cells, cell entry into S‐phase was completely inhibited. To investigate the mode of cell‐cycle inhibition, analysis was done of the possible role of early Na + fluxes in the mitogenic signal transduced from cell membrane receptors to the nucleus. The effects of the two drugs amiloride and bumetanide on induction of three genes‐c‐fos, c‐myc, and ornithin decarboxylase (ODC)‐was measured during cell transition through the G<jats:sub>1</jats:sub>‐phase. Amiloride and bumetanide, when added separately or in combination, did not inhibit the induction of c‐fos, c‐myc, and ODC mRNAs. These results suggest that stimulation of Na<jats:sup>+</jats:sup> fluxes by serum growth factors is essential for cell transition into the S‐phase of cell cycle, but it plays no apparent role in the growth factor signal transduced from the cell surface to the interior of the cell, as manifested by c‐fos, c‐myc, and ODC genes induction.</jats:p>