Growth factors activate the Na+/H+ antiporter in quiescent fibroblasts by increasing its affinity for intracellular H+.
Growth factors (alpha-thrombin and insulin) activate a Na+/H+ antiport in G0/G1-arrested Chinese hamster lung fibroblasts (CCL39). In this report, we have examined 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. Our results indicate the following. 1) In quiescent as in mitogen-stimulated cells, Na+/H+ antiport is regulated by internal H+ in an allosteric way, whereas, in contrast, interactions with external H+ and Na+ obey simple saturation kinetics. 2) The growth factor-induced activation of Na+/H+ exchange, which, under physiological conditions, is responsible for a sustained cytoplasmic alkalinization, is due to an increased affinity for internal H+ (the apparent pK is shifted by approximately 0.3 pH unit towards alkaline pH values). Therefore, we propose that growth factors promote a conformational change of the Na+/H+ antiporter, possibly at the level of an internal modifier site(s).
D000584:Amiloride / Q000494:pharmacology; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D001565:Benzoates; D019817:Benzoic Acid; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008168:Lung; D017923:Sodium-Hydrogen Exchangers; D013917:Thrombin / Q000494:pharmacology*
D001565:Benzoates; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D006133:Growth Substances; D017923:Sodium-Hydrogen Exchangers; D000641:Ammonia; D000584:Amiloride; D019817:Benzoic Acid; D013917:Thrombin