Maturational changes in rabbit renal brush border membrane vesicle urea permeability

Urea transport in the proximal tubule is thought to occur by passive diffus ion through the lipid bilayers of the cell membranes. The lipid composition of cell membranes changes during maturation and may directly affect urea p ermeability of proximal tubule membranes. The present study examined the ma turation of urea transport in rabbit renal brush border membrane vesicles ( BBMV). BBMV from adult and neonatal (9- to 11-d-old) New Zealand white rabb its were loaded with 500 mM urea and mixed with an iso-osmotic mannitol sol ution using a stop-flow instrument. Vesicle shrinkage, due to efflux of ure a, was followed with light scattering and urea permeability was calculated from an exponential fit of the data. Urea permeability was significantly lo wer in the neonatal BBMV than the adult at 25 degrees C (0.34 +/- 0.04 x 10 (-6) versus 0.56 +/- 0.03 x 10(-6) cm/sec; p < 0.001, n = 7) and 37 degrees C (0.45 +/- 0.04 x 10(-6) versus 0.66 +/- 0.03 x 10(-6) cm/sec; p = 0.001, n = 7). There was no effect of 250 mu M phloretin on urea permeability in either adult or neonatal BBMV at either temperature. The activation energy for urea diffusion was higher in the neonatal than the adult BBMV. Because the maturational increase in urea permeability could potentially be due to a sodium-dependent urea transporter in the adult BBMV, the sodium dependenc e of urea uptake in adult BBMV was examined. There was no difference in ure a permeability in the presence or absence of 20 mM NaCl. Permeability of th e lipid-soluble molecule, glycerol, was also found to be the same in the ne onatal and adult BBMV. Urea transport in the apical membrane of neonatal an d adult proximal tubules is not phloretin sensitive, a finding consistent w ith diffusion of urea via the lipid bilayer. The rare of urea diffusion is lower in neonatal membranes and may be an important factor in overall urea excretion. This may also play a role in developing and maintaining a high m edullary urea concentration and thus the ability to concentrate the urine d uring renal maturation.