The renal cortical collecting duct (CCD) consists of principal and intercalated cells. Two forms of intercalated cells, those cells involved in H+/HCO3- transport, have recently been described. H+-secreting cells are capable of apical endocytosis and have H+ATPase on the apical membrane and a basolateral Cl-/HCO3- exchanger. HCO3(-)-secreting cells bind peanut agglutinin (PNA) to apical membrane receptors and have diffuse or basolateral distribution of H+ATPase; their Cl-/HCO3- exchanger is on the apical membrane. We found that 20 h after acid feeding of rabbits, there was a fourfold increase in number of cells showing apical endocytosis and a numerically similar reduction of cells binding PNA. Incubation of CCDs at pH 7.1 for 3-5 h in vitro led to similar, albeit less pronounced, changes. Evidence to suggest internalization and degradation of the PNA binding sites included a reduction in apical binding of PNA, decrease in pH in the environment of PNA binding, and incorporation of electron-dense PNA into cytoplasmic vesicles. Such remodeling was dependent on protein synthesis. There was also functional evidence for loss of apical Cl-/HCO3- exchange on PNA-labeled cells. Finally, net HCO3- flux converted from secretion to absorption after incubation at low pH. Thus, exposure of CCDs to low pH stimulates the removal/inactivation of apical Cl-/HCO3- exchangers and the internalization of other apical membrane components. Remodeling of PNA-labeled cells may mediate the change in polarity of HCO3- flux observed in response to acid treatment.

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