Role of renal aquaporins in escape from vasopressin-induced antidiuresis in rat.
The purpose of this study was to investigate whether escape from vasopressin-induced antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semiquantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. The results suggest that escape from vasopressin-induced antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin-2 water channel expression in the renal collecting duct.
Ecelbarger
C A
CA
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nielsen
S
S
Olson
B R
BR
Murase
T
T
Baker
E A
EA
Knepper
M A
MA
Verbalis
J G
JG
D000818:Animals; D051399:Aquaporin 2; D051400:Aquaporin 3; D051403:Aquaporin 6; D020346:Aquaporins; D001483:Base Sequence; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects* / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology; D014867:Water / Q000378:metabolism
C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D017931:DNA Primers; D007473:Ion Channels; D012333:RNA, Messenger; D012076:Renal Agents; D014867:Water; D051400:Aquaporin 3; D003894:Deamino Arginine Vasopressin