title: Vasopressin increases urea permeability in the initial IMCD from diabetic rats.
abstract: In normal rats, vasopressin and hyperosmolality enhance urea permeability (P(urea)) in the terminal, but not in the initial inner medullary collecting duct (IMCD), a process thought to occur through the UT-A1 urea transporter. In the terminal IMCD, UT-A1 is detected as 97- and 117-kDa glycoproteins. However, in the initial IMCD, only the 97-kDa form is detected. During streptozotocin-induced diabetes mellitus, UT-A1 protein abundance is increased, and the 117-kDa UT-A1 glycoprotein appears in the initial IMCD. We hypothesize that the 117-kDa glycoprotein mediates the vasopressin- and osmolality-induced changes in P(urea). Thus, in the present study, we measured P(urea) in in vitro perfused initial IMCDs from diabetic rats by imposing a 5 mM bath-to-lumen urea gradient without any osmotic gradient. Basal P(urea) was similar in control vs. diabetic rats (3 +/- 1 vs. 5 +/- 1 x 10(-5) cm/s, n = 4, P = not significant). Vasopressin (10 nM) significantly increased P(urea) to 16 +/- 5 x 10(-5) cm/s (n = 4, P < 0.05) in diabetic but not in control rats. Forskolin (10 microM, adenylyl cyclase activator) also significantly increased P(urea) in diabetic rats. In contrast, increasing osmolality to 690 mosmol/kg H2O did not change P(urea) in diabetic rats. We conclude that initial IMCDs from diabetic rats have vasopressin- and forskolin-, but not hyperosmolality-stimulated P(urea). The appearance of vasopressin-stimulated P(urea) in initial IMCDs correlates with an increase in UT-A1 protein abundance and the appearance of the 117-kDa UT-A1 glycoprotein in this region during diabetes. This suggests that the 117-kDa UT-A1 glycoprotein is necessary for vasopressin-stimulated urea transport.
authors.affiliation: Emory Univ. School of Medicine, Renal Division, 1639 Pierce Dr., NE, WMB Rm. 338, Atlanta, GA 30322, USA. vpech@emory.edu
authors.forename: Vladimir
authors.initials: V
authors.lastname: Pech
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: Shelley D
authors.initials: SD
authors.lastname: Kozlowski
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wall
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Sands
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose; D002463:Cell Membrane Permeability / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003928:Diabetic Nephropathies / Q000378:metabolism*; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*; D000096982:Urea Transporters
chemical_list: D001786:Blood Glucose; D005576:Colforsin; D026901:Membrane Transport Proteins; D012076:Renal Agents; D014508:Urea; D014667:Vasopressins; D000096982:Urea Transporters