The Renal Handling of Biologically Active Peptides

The site of protein elimination and degradation is until now not exactly known. The reticulo-endothelial system may play a major role (Ehrenreich nd Cohn, 1967). Emphasis has been put on the kidney as an organ for the elimination and catabolism of proteins, but data on plasma disappearance after bilateral nephrectomy of, for example, albumin, IgG or transferrin (Sewrd nd Morgn, 1970; Rosenfeld et l., 1962) show clearly that the kidney plays no more than a minor role in the elimination of these proteins. Studies on the arteriovenous balance of -amino-nitrogen across the kidney failed to reflect significant proteolysis (Elisch et l., 1955). However several exceptions from this statement must be made: (1) Overlod of the kidney with a protein, due to glomerular diseases leads to an accumulation within proximal tubular cells and subsequent degradation. (2) Exogenous proteins such as Staphylococcal Enterotoxin B (Normn nd Stone, 1972) or endogenous pthologicl proteins such as the Bence Jones protein (Wochner et l., 1967) are rapidly taken up by the kidney and degraded, provided their molecular weight allows the passage through the glomerular filter. Experiments with intraluminal injections of various foreign proteins horseradish peroxidase, ferritin demonstrated the absorptive capability of the proximal tubule cells for proteins that usually do not appear in the primary urine. (3) The kidney is the major site of elimination and degradation for the peptide hormones: insulin and glucagon (Nhr et l., 1958); human chorionic gonadotrophin (Collip et l., 1966); growth hormone and luteinizing hormone (De Kretser et l., 1969); luteinizing hormone releasing hormone (Miychi et al., 1973), and prolactin (Rjniemi et al., 1974) have been shown to accumulate in the kidney cortex. All these hormones have very short half-lives of several minutes as they are rapidly catabolized in the kidney. This process warrants the rapid removal rates necessary for components of biological feedback mechanisms.