Tubular handling of neurotensin in the rat kidney as studied by micropuncture and HPLC
Bjerke, T.; Christensen, E.I.; Boye, N.
American Journal of Physiology 256(1 Pt 2): F100-F106
1989
ISSN/ISBN: 0002-9513 PMID: 2912155 Document Number: 342512
Micropuncture studies were performed to assess the reabsorption and metabolism of the vasoactive peptide neurotensin (NT) in individual nephron segments and compare it to the handling of the closely related peptide bradykinin (BK). Rat proximal and distal convoluted tubules were microinfused with [3H]NT or [3H]BK. In a second set of experiments, [3H]NT and its metabolites in the ureteral urine were separated and characterized using high-performance liquid chromatography (HPLC) technique. The urinary recovery of 3H-labeled material was 31% when proximal tubules were microinfused with [3H]NT and 94% when distal tubules were infused. For proximal tubules the label recovered in the ureteral urine consisted exclusively of metabolites of NT and appeared as tyrosine, NT1-11, probably NT9-13, and two uncharacterized products. For distal tubules, 9% chromatographed as intact NT in the urine and except for the proportion the metabolites were almost identical to those found when proximal tubules were microinfused. Following microinfusion of [3H]BK into proximal tubules, the urinary recovery of 3H-labeled material was 19%. There was no correlation between fractional reabsorption of 3H-labeled material and proximal tubular length when [3H]NT or [3H]BK was microinfused. In vitro incubation studies with rat ureteral urine showed extensive degradation of NT yielding tyrosine, NT1-6, probably NT9-13, NT, and two uncharacterized products. In contrast, there was no detectable breakdown of BK over a 32-min period. Finally, [3H]NT was incubated in rat serum, and these experiments also showed degradation of the peptide but not to the extent as when incubated in ureteral urine. The present study suggests that NT and BK fragments are reabsorbed in the proximal tubule, most likely mainly in the pars recta. In addition, enzymes in the tubular fluid probably play an important role in digestion of NT but not BK.