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The kidney plays a key role in the metabolism of neurotensin (NT). We have examined the renal mechanisms of NT clearance by measuring plasma NT basally and after 45 min infusion of NT(1-13) in intact rats, anephric rats (no glomerular filtration, no peritubular metabolism) and ureteral ligated rats (reduced filtration). Plasma NT was measured by radioimmunoassay with both C (biologically active end) and N terminal directed antisera. In anephric and ureteral ligated rats, basal plasma NT like immunoreactivity measured with either antisera was increased 3-fold compared with unoperated rats. C terminal concentrations were higher than N indicating that a C terminal variant of NT was present in basal plasma. Infusion of NT(1-13) increased N terminal NT from 36 +/- 3 to 249 +/- 35 pmol/l (p less than 0.01) in unoperated rats with significantly larger increases in the renally compromised groups. This was reflected in the reduced metabolic clearance rates (measured with the N terminal directed antisera) in the anephric (16 +/- 1 ml/kg/min) and ureteral ligated (17 +/- 3 ml/kg/min) rats when compared with the control rats (26 +/- 4 ml/kg/min). The similar reductions in the anephric and ureteral ligated rats suggested that the decrease in N terminal NT metabolism was from the absence of filtration. Infusion of NT did not increase C terminal NT immunoreactivity in intact, anephric and ureteral ligated rats showing that the C terminal end was extremely labile. However when endogenous converting enzyme activity was blocked by captopril administration there was a significant increase in C terminal immunoreactivity suggesting a role for converting enzyme like proteases in the clearance of the biologically active end of NT.(ABSTRACT TRUNCATED AT 250 WORDS) |
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