GROWTH-FACTORS ACTIVATE THE NA+/H+ ANTIPORTER IN QUIESCENT FIBROBLASTS BY INCREASING ITS AFFINITY FOR INTRACELLULAR H+

Abstract

Growth factors (.alpha.-thrombin and insulin) activate a Na+/H+ antiport in G0/G1-arrested Chinese hamster lung fibroblasts (CCL39). The influence of intracellular pH on this exchange activity, measured by initial rates of amiloride-sensitive 22Na+ uptake, in the absence and presence of growth factors was investigated. In quiescent as in mitogen-stimulated H+ in an allosteric way, whereas, in contrast, interactions with external H+ and Na+ obey simple saturation kinetics. The growth factor-induced activation of Na+/H+ exchange, which is responsible for a sustained cytoplasmic alkalinization, is due to an increased affinity for internal H+ (the apparent pK is shifted by .apprx. 0.3 pH unit towards alkaline pH values). It is proposed that growth factors promote a conformational change of the Na+/H+ antiporter, possibly at the level of an internal modifier site(s).