Glutamine synthesis is heterogeneous and differentially regulated along the rabbit renal proximal tubule

Glutamine synthesis, a major process for ammonia detoxification and the con trol of acid-base balance, occurs from various precursors in suspensions of rabbit proximal tubules. However, no data are currently available on the d istribution of glutamine synthesis along the rabbit proximal tubule, and it s modulation by changes of substrate concentration. Therefore we have micro dissected and incubated the three parts (S1, S2 and S3) of rabbit proximal tubules and measured glutamine synthesis from alanine and aspartate. With a physiological concentration of alanine (0.25 mM) or aspartate (0.05 mM), g lutamine synthesis in the S1 segment was about half of that in the S2 and S 3 segments, and was greater from alanine than from aspartate along the enti re proximal tubule. Elevation of alanine and aspartate concentrations to 5 mM increased glutamine synthesis in both a substrate- and segment-dependent manner. It is concluded that glutamine synthesis occurs from alanine and a spartate along the entire rabbit proximal tubule; however, contrary to what might have been expected on the basis of measurement of glutamine syntheta se activity, the basal rate of glutamine synthesis and its adaptation to in creased substrate availability are heterogeneous along this nephron segment .