Diminished expression of aquaporin water channels in ureteral-obstructed kidney in rats.
OBJECTIVE
We investigated whether regulation of aquaporin (AQP) water channels is altered in the ureteral-obstructed kidney.


METHODS
Male Sprague-Dawley rats were unilaterally obstructed of their left proximal ureters for 48 h. The protein expression of AQP1-3 channels was determined in the kidney by Western blot analysis. The expression of AQP2 was also determined by immunohistochemistry. In order to specifically determine primary impairment of the pathway leading to an altered regulation of AQP channels stimulated by the arginine vasopressin (AVP)/cyclic adenosine monophosphate (cAMP) pathway, the catalytic activity and protein expression of different parts of the adenylyl cyclase complex were separately determined.


RESULTS
In the previously obstructed kidney, urinary osmolality and free water reabsorption were greatly decreased. The expression of AQP2 proteins was decreased in the cortex, outer medulla and inner medulla. Immunohistochemistry also showed a marked decrease in AQP2 expression. The expression of AQP1 and AQP3 was decreased in the outer medulla and inner medulla. cAMP generation in response to AVP, sodium fluoride or forskolin was greatly decreased. The expression of Gsalpha and adenylyl cyclase VI proteins was decreased. The contralateral kidney showed minimal or no changes in these parameters.


CONCLUSIONS
The reduced abundance of AQP water channels may at least partly account for the urinary concentration defect in the ureteral-obstructed kidney. The primary point of impairment of AQP channels regulated by the AVP/cAMP pathway may lie at the level of the catalytic unit of adenylyl cyclase.
Department of Internal Medicine, Cheju National University Medical School, Jeju, South Korea.
Chung Ho
CH
Yeum
Soo Wan
SW
Kim
Seong Cheol
SC
Lee
Ki Chul
KC
Choi
Kyu Youn
KY
Ahn
JongUn
J
Lee
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D051400:Aquaporin 3; D020346:Aquaporins / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000378:metabolism*
C496029:Aqp3 protein, rat; D020346:Aquaporins; D001127:Arginine Vasopressin; D051400:Aquaporin 3; D000262:Adenylyl Cyclases