Carrier-mediated transport of pyroglutamyl-histidine in renal brush border membrane vesicles

• Published in: The American journal of physiology Vol. 255; no. 6 Pt 1; p. C822
• Main Authors: Skopicki, H A, Fisher, K, Zikos, D, Flouret, G, Bloch, R, Kubillus, S, Peterson, D R
• Format: Journal Article
• Language: English
• Published: United States 01.12.1988
• Subjects: Animals; Biological Transport, Active - drug effects; Dipeptides - metabolism; Hydrogen-Ion Concentration; Kidney - metabolism; Kidney Cortex - metabolism; Kidney Tubules, Proximal - metabolism; Kinetics; Microvilli - drug effects; Microvilli - metabolism; Oligopeptides - pharmacology; Pyrrolidonecarboxylic Acid - analogs & derivatives; Rabbits; Sodium - pharmacology
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1988.255.6.c822

These studies were performed to determine if a transmembrane carrier for pyroglutamyl-histidine (pGlu-His) is present in the luminal membrane of renal proximal tubular cells. Previous studies have suggested the intact transepithelial transport of pGlu-His, a dipeptide formed by the hydrolysis of luteinizing hormone-releasing hormone by enzymes associated with the brush border in the proximal nephron. With the use of a renal brush border membrane vesicle preparation, pGlu-His showed H+-stimulated, Na-independent, saturable transport into an osmotically active space. High-pressure liquid chromatographic analysis of both the intravesicular and extravesicular fluids indicated intact uptake of the dipeptide. The transport constant (Kt) and Vmax for pGlu-His transport were 9.3 X 10(-8) M and 6.1 X 10(-12) mol.mg-1.min-1, respectively. Transport of pGlu-His was not inhibited by the dipeptides glycyl-proline, glycyl-sarcosine, and N-beta-alanyl-L-histidine, which have been previously shown to be transported into renal brush border vesicles via a single, low-affinity, high-capacity, Na-independent, and H+-stimulated peptide carrier. In addition, the gamma-glutamyl-containing peptides gamma-glutamyl-histidine and N(N-L-gamma-glutamyl-L-cysteinyl)glycine and the tripeptide pyroglutamyl-histidyl-prolinamide were without an inhibitory effect. In contrast, transport of pGlu-His was inhibited by the dipeptide pyroglutamyl-alanine. This study demonstrates the existence of a high-affinity, low-capacity H+ cotransport system for pGlu-His in the proximal tubular luminal plasmalemma, which appears to be specific for pyroglutamyl-containing dipeptides. The data indicate that multiple dipeptide carriers are present in the proximal nephron.