Vasopressin increases urea permeability in the initial IMCD from diabetic rats.
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.
Pech
Vladimir
V
Emory Univ. School of Medicine, Renal Division, 1639 Pierce Dr., NE, WMB Rm. 338, Atlanta, GA 30322, USA. vpech@emory.edu
Klein
Janet D
JD
Kozlowski
Shelley D
SD
Wall
Susan M
SM
Sands
Jeff M
JM
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
D001786:Blood Glucose; D005576:Colforsin; D026901:Membrane Transport Proteins; D012076:Renal Agents; D014508:Urea; D014667:Vasopressins; D000096982:Urea Transporters