title: Glucocorticoids increase osmotic water permeability (Pf) of neonatal rabbit renal brush border membrane vesicles.
abstract: During postnatal maturation, there is an increase in renal brush border membrane vesicle (BBMV) osmotic water permeability and a parallel increase in aquaporin-1 (AQP1) protein abundance. The mechanisms responsible for these changes remain unknown. Because serum glucocorticoid levels rise postnatally and have previously been linked to other maturational changes in renal function, we examined the effects of glucocorticoids on osmotic (Pf) and diffusional (P(DW)) water permeability and AQP1 protein abundance of renal BBMV. Neonatal rabbits were treated with dexamethasone (10 microg/100 g) for three days and compared with control neonates and adults. Pf and P(DW) were measured at 20 degrees C with a stopped-flow apparatus using light-scattering and aminonaphthalene trisulfonic acid (ANTS) fluorescence, respectively. Pf was significantly higher in BBMV from dexamethasone-treated neonates compared with vehicle-treated neonates, but remained lower than in BBMV from adults (P<0.05). P(DW) in dexamethasone and vehicle-treated neonatal BBMV was lower than in adult BBMV. Pf/P(DW) ratio increased from neonate (5.1+/-0.3) to dexamethasone (7.0+/-0.1) and adult BBMV (6.3+/-0.1). AQP1 expression was increased by dexamethasone treatment to adult levels. Membrane fluidity, which is inversely related to generalized polarization (GP) of steady-state laurdan fluorescence, was significantly higher in neonatal BBMV than both dexamethasone and adult BBMV (GP: neonate 0.285+/-0.002, dexamethasone treatment 0.302+/-0.006, and adult 0.300+/-0.005; P<0.05). These combined results show that dexamethasone-treatment during days 4-7 of life increases BBMV water permeability despite a decrease in membrane fluidity. This occurs by increasing channel-mediated water transport, as reflected in an increase in AQP1 protein abundance and a higher Pf/P(DW) ratio. This mimics the maturational changes and suggests a physiological role for glucocorticoids in maturation of proximal tubule water transport.
authors.affiliation: Dept. of Pediatrics, U. T. Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA.
authors.forename: Jaap
authors.initials: J
authors.lastname: Mulder
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Maha N
authors.initials: MN
authors.lastname: Haddad
authors.forename: Michel
authors.initials: M
authors.lastname: Baum
authors.forename: Raymond
authors.initials: R
authors.lastname: Quigley
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology*; D051398:Aquaporin 1; D020346:Aquaporins / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D014867:Water / Q000378:metabolism*
chemical_list: D020346:Aquaporins; D005938:Glucocorticoids; D014867:Water; D051398:Aquaporin 1; D003907:Dexamethasone