Renal handling of luteinizing hormone releasing hormone: a model for peptide transport and hydrolysis.
This study provides evidence that: 1) LHRH is degraded by renal brush border hydrolases, followed by reabsorption of oligopeptide metabolites in the proximal kidney tubule. 2) Peptide carriers are present in the luminal membrane of the proximal nephron, which apparently function to reabsorb oligopeptide metabolites resulting from hydrolysis of filtered peptides, including LHRH. 3) Renal brush border hydrolysis of LHRH involves cleavage at multiple sites by endopeptidases like angiotensin I-converting enzyme and endopeptidase 24.11; D-amino acid substituents at these sites may alter the expected cleavage pattern of the analogs. 4) A transcytotic pathway is present in the proximal nephron which is facilitated by endocytosis of cationic macromolecules; such a pathway may function to reabsorb hydrolytically resistant peptides, but the issue of potential toxicity must be clarified.
Peterson
D R
DR
Department of Physiology, University of Health Sciences/Chicago Medical School, Illinois 60064.
Skopicki
H A
HA
Zikos
D
D
Flouret
G
G
D000042:Absorption; D000818:Animals; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006867:Hydrolases / Q000378:metabolism; D006868:Hydrolysis; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D015260:Neprilysin; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011817:Rabbits
D004151:Dipeptides; D007987:Gonadotropin-Releasing Hormone; D006867:Hydrolases; D007703:Peptidyl-Dipeptidase A; D008666:Metalloendopeptidases; D015260:Neprilysin