Adaptive regulation of taurine and β-alanine uptake in a human kidney cell line from the proximal tubule

Abstract

1. The underlying mechanisms involved in the adaptive regulation of β-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine homeostasis occurs predominantly via changes in the activity of the high-affinity taurine transport system by alterations in the uptake capacity and with an unaffected half-saturation constant. An adaptive response was not observed for the structurally related β-alanine. 3. Only colchicine, which interferes with microtubule organization, was capable of blocking the response to alterations of taurine in cell medium, whereas inhibition of protein and nucleic acid synthesis by cycloheximide and actinomycin D, respectively, did not change the adaptive pattern. 4. Phorbol 12-myristate 13-acetate (PMA), mimicking the effects of diacylglycerol, induced inhibition of both β-alanine and taurine uptake. By contrast, the Ca 2+-ionophore A23187, mimicking the effects of IP 3, only stimulated the uptake of taurine but not the influx of β-alanine. However, the effect of PMA down-regulation and A23187 up-regulation was rapid and short-lived in contrast to the adaptive response, suggesting that the inositol phospholipid pathway involving diacetylglycerol and IP 3 is less likely to be linked directly to the adaptive regulation, but rather plays a role in short-term regulation.