Ganz M B, Boyarsky G, Sterzel R B, Boron W F
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06511.
Nature. 1989 Feb 16;337(6208):648-51. doi: 10.1038/337648a0.
Growth factors raise intracellular pH (pHi) by stimulating Na+/H+ exchange in the absence of HCO3-. In mutant cells that lack the Na+/H+ exchange activity, this alkalinization does not occur, and the cells do not proliferate without artificial elevation of pHi. It has therefore been widely suggested that an early pHi increase is a necessary signal for mitogenesis. In the presence of HCO3- however, growth factors fail to raise pHi in A431 cells, renal mesangial cells and 3T3 fibroblasts. In mesangial cells, arginine vasopressin (AVP) raises pHi in the absence of HCO3-, but lowers it when HCO3- is present; growth is stimulated under both conditions. We report here that, in the presence of HCO3-, AVP stimulates two potent HCO3- transporters, as well as the Na+/H+ exchanger. These are the Na+-dependent and Na+-independent Cl-/HCO3- exchangers. Our results indicate that AVP causes acidification in the presence of HCO3- because, at the resting pHi, it stimulates Na+-independent Cl-/HCO3- exchange (which lowers pHi) more than it stimulates the sum of Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange (both of which raise pHi). The stimulation of three acid-base transporters by the growth factor AVP greatly enhances the ability of the cell to regulate pHi.
生长因子在没有HCO₃⁻的情况下通过刺激Na⁺/H⁺交换来提高细胞内pH值（pHi）。在缺乏Na⁺/H⁺交换活性的突变细胞中，这种碱化不会发生，并且在没有人为提高pHi的情况下细胞不会增殖。因此，人们普遍认为早期pHi升高是有丝分裂的必要信号。然而，在有HCO₃⁻存在的情况下，生长因子无法在A431细胞、肾系膜细胞和3T3成纤维细胞中提高pHi。在系膜细胞中，精氨酸加压素（AVP）在没有HCO₃⁻的情况下会提高pHi，但在有HCO₃⁻存在时会降低pHi；在这两种情况下生长都会受到刺激。我们在此报告，在有HCO₃⁻存在的情况下，AVP会刺激两种有效的HCO₃⁻转运体以及Na⁺/H⁺交换体。它们是Na⁺依赖性和Na⁺非依赖性Cl⁻/HCO₃⁻交换体。我们的结果表明，AVP在有HCO₃⁻存在时会导致酸化，因为在静息pHi时，它刺激Na⁺非依赖性Cl⁻/HCO₃⁻交换（会降低pHi）的程度超过它刺激Na⁺/H⁺交换和Na⁺依赖性Cl⁻/HCO₃⁻交换（两者都会提高pHi）的总和。生长因子AVP对三种酸碱转运体的刺激极大地增强了细胞调节pHi的能力。
