Glycylsarcosine uptake in rabbit renal brush border membrane vesicles isolated from outer cortex or outer medulla: evidence for heterogeneous distribution of oligopeptide transporters.

Abstract

Studies were initially performed in rabbit brush border membrane vesicles (BBMV) prepared from whole cortex plus outer medulla. In these studies using combined tissues, two distinct peptide/H+transport systems were found for glycylsarcosine (GlySar) uptake, with one representing a low-affinity/high-capacity system (Vm1 = 974 pmol/mg/10 sec and Km1 = 4819 microM) and the other a high-affinity/low-capacity system (Vm2 = 220 pmol/mg/10 sec and Km2 = 96 microM). Thus, under linear conditions, the high-affinity transporter accounted for about 92% of the total transport of dipeptide. To better define the regional heterogeneity of peptide transporter activity in kidney, subsequent studies were performed in vesicles prepared from separately harvested outer cortical and outer medullary tissue. In BBMV studies prepared from outer cortex, two saturable components were revealed for GlySar transport (low-affinity/high-capacity transport system: Vm1 = 1921 pmol/mg/10 sec and Km1 = 11714 microM; high-affinity/low-capacity transport system: Vm2 = 143 pmol/mg/10 sec and Km2= 138 microM). However, in BBMV studies prepared from outer medulla, only one saturable component was revealed for GlySar transport (high-affinity/low-capacity transport system:Vm2= 168 pmol/mg/10 sec and Km2 = 230 microM). Overall, these studies support the contention that peptides are handled sequentially in kidney (ie, first by low-affinity transporter PEPT1, and then by high-affinity transporter PEPT2) and that PEPT2 is primarily responsible for the renal reabsorption of peptides and peptidomimetics.