Physiologic and Pathophysiologic Roles of Aquaporin Water Channels in Rat Kidney.
- Author:
Soo Wan KIM
1
;
Jong Un LEE
;
Chung Ho YEUM
;
Myong Yun NAH
;
Nam Ho KIM
;
Ki Chul CHOI
Author Information
1. Departments of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. skimw@chonnam.ac.kr
- Publication Type:Original Article
- MeSH:
Mice;
Rats;
Animals
- From:Korean Journal of Nephrology
2001;20(5):785-801
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Recent discovery of aquaporin(AQP) water channels has advanced our understanding of water transport in the kidney. They play an important role in the urinary concentration through generation of medullary hypertonicity and regulation of collecting duct water permeability. Among multiple isoforms of AQP family, AQP1 is highly expressed in the proximal tubule and descending thin limb. The critical role of AQP1 has been confirmed in transgenic mice lacking AQP1 that are unable to concentrate the urine and severely dehydrated. The abundance of AQP2 is highly expressed in the principal cell of the collecting duct. It is short-term and long-term regulated by AVP/cAMP pathway to increase the osmotic water reabsorption. The short-term regulation of AQP2 channels occurs as a result of an exocytic insertion of the cytoplasmic AQP2 vesicles into the apical membrane, whereas the long-term effect is to increase the total abundance of AQP2 proteins. Water reabsorption across the basolateral membrane of the collecting duct is in turn mediated by AQP3 and AQP4. An altered regulation of AQP channels in the kidney has been known in various pathophysiological situations. A reduced abundance of AQP water channels may at least in part account for the impaired urinary concentration in the ischemic acute renal failure and cisplatin-, gentamicin-, and amphotericin B-induced nephropathy. The postobstructive diuresis has been attributed to a decreased expression of AQP1-4 proteins in the obstructed kidney. In these situations, however, the primary impairment in the pathway leading to the generation of cAMP and hence the expression of cAMP-mediated AQP chan nels lies at the level of G proteins and/or at the catalytic unit of adenylyl cyclase. On the other hand, following the treatment with deoxycorticosterone or NG-nitro-L-arginine methyl ester, the expression of AQP2 proteins was increased in the kidney, in association with an augmented adenylyl cyclase activity. In two-kidney, one clip hypertension, the total abundance of AQP2 proteins was significantly decreased in the clipped kidney, while their trafficking remained unaltered. Concomitantly with the reversal of the blood pressure following removal of the renal arterial clip, the abundance of AQP2 expression returned to the control level. The AVP-evoked cAMP generation was decreased in the clipped kidney, and returned to the control value following removal of the clip. Following the treatment with 0.04% methimazole, the expression of AQP2 protein was increased in the kidney, in association with hyponatremia. An altered regulation of AQP water channels in the kidney may be causally related to various pathophysiological situations associated with altered urinary concentration ability and water retention.
