Excretion of progastrin products in human urine.
The renal handling of carboxyamidated gastrins, NH2-terminal progastrin fragments, and glycine-extended gastrins was examined in healthy volunteers. The respective urinary clearances after a meal amounted to 0.09 +/- 0.02%, 0.17 +/- 0.04% (P < 0.05), and 0.04 +/- 0.01% (P < 0.01) of the glomerular filtration rate. During intravenous infusion of carboxyamidated gastrin-17, progastrin fragment-(1-35), and glycine-extended gastrin-17, the respective urinary clearances amounted to 0.08 +/- 0.02, 0.46 +/- 0.08, and 0. 02 +/- 0.01%, respectively, of the glomerular filtration rate. The metabolic clearance rate of the three peptides was 24.4 +/- 1.3, 6.0 +/- 0.4, and 8.6 +/- 0.7 ml. kg-1. min-1. A maximum rate for tubular transport or degradation of the peptides could not be determined, nor was a renal plasma threshold recorded. Plasma concentrations and urinary excretion rates correlated for gastrin-17 and progastrin fragment-(1-35) (r = 0.94 and 0.97, P < 0.001), whereas the excretion of glycine-extended gastrin diminished with increasing plasma concentrations. We conclude that renal excretion of progastrin products is negligible compared with renal metabolism and that renal handling of the peptides depends on their molecular structure. Hence, the kidneys exhibited a higher excretion of NH2-terminal progastrin fragments than of carboxyamidated and especially glycine-extended gastrins.
Hansen
C P
CP
Departments of Gastrointestinal Surgery and Clinical Biochemistry, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Goetze
J P
JP
Stadil
F
F
Rehfeld
J F
JF
D001711:Biotransformation; D005755:Gastrins / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine*; D005919:Glomerular Filtration Rate; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000502:physiology*; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D011498:Protein Precursors / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D011863:Radioimmunoassay; D012016:Reference Values; D012044:Regression Analysis; D013997:Time Factors
D005755:Gastrins; D010446:Peptide Fragments; D011498:Protein Precursors; C118842:progastrin (1-35); C013706:big gastrin; C013550:gastrin 17