Regulation of Collecting Duct Water Channel Expression by Vasopressin in Brattleboro Rat
| Title: | Regulation of Collecting Duct Water Channel Expression by Vasopressin in Brattleboro Rat |
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| Authors: | DiGiovanni, Susan R.; Nielsen, Soren; Christensen, Erik Ilso; Knepper, Mark |
| Publisher: | Proceedings of the National Academy of Sciences of the U.S.A |
| Date Published: | September 13, 1994 |
| Reference Number: | 359 |
AQP-CD is a vasopressin-regulated water channel expressed exclusively in the renal collecting duct. We have previously shown that AQP-CD is present in the apical plasma membrane and subapical vesicles of collecting duct cells, consistent with membrane-shuttling mechanisms that have been proposed to explain the short-term action of [Arg8] vasopressin (AVP) to regulate apical water permeability. We propose here that AVP may also have long-term actions on the collecting duct to regulate the expression of the AQP-CD water channel. We used immunoblotting, immunohistochemistry, and in vitro perfusion of renal tubules to investigate water channel regulation in collecting ducts of diabetes insipidus (Brattleboro) rats treated with a 5-day infusion of AVP or vehicle. Immunoblotting and immunohistochemistry demonstrated that collecting ducts of vehicle-infused Brattleboro rats had markedly reduced expression of AQP-CD relative to normal rats. In response to AVP infusion there was a nearly 3-fold increase in AQP-CD expression as detected by immunoblotting. Immunocytochemistry demonstrated that the increased expression was predominantly in the apical plasma membrane and subapical vesicles of collecting duct cells. Inner medullary collecting ducts of AVP-infused Brattleboro rats displayed a 3-fold increase in osmotic water permeability relative to vehicle-infused controls, in parallel with the change in AQP-CD expression. Based on these findings, we conclude that (i) long-term infusion of AVP, acting either directly or indirectly, regulates expression of the AQP-CD water channel and (ii) AQP-CD is the predominant AVP-regulated water channel.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
But AQP-CD cannot increase the apical membrane Pf without first being signaled to do so by the antidiuretic hormone, arginine vasopressin (AVP). There is much evidence to support the notion that AVP regulates the Pf of the apical membrane in the short-term. That is, when AVP is present, AQP-CDs are inserted into the apical membrane, increasing its Pf; when AVP absents itself from the cell, AQP-CDs are removed from the apical membrane, returning its Pf to its normal low level.
DiGiovanni, et al., propose that AVP may also regulate apical membrane Pf in the long-term through its effect on AQP-CD. They investigated AQP-CD regulation in the CDs of a breed of rats with low circulating levels of AVP. They installed a mini-pump in each of the rats in the experimental group. Then for 5 days the pump pumped AVP into their systems. This 5-day infusion resulted in a 3-fold increase in AQP-CD expression in the principal cells. This increase occurred in the cell's apical membrane and subapical regions.
In contrast, the rats in the control group, still having no circulating AVP, showed no increase in AQP-CD. Their AQP-CD level continued to be much lower than normal rats, as would be expected since this breed of rat is incapable of synthesizing or circulating AVP.
The authors then took the IMCD tissue from both rat groups, added AVP to it, and measured to see the effect on IMCD Pf. In both groups the infusion of AVP significantly increased Pf. However, the Pf increase in the experimental group (the rats that were infused with AVP for 5 days) increased 3-fold. This paralleled their 3-fold increase in AQP-CD expression. The authors conclude that AVP has both a short-term and long-term effect to increase Pf in the IMCD by regulating AQP-CD expression. Whether AVP regulates AQP-CD's expression directly or indirectly could not be determined by their test. Their test did, however, determine that AQP-CD is the predominant AVP-regulated water channel in the kidney CD.
The mechanism involved in AVP-mediated increase in AQP-CD expression is as yet unknown. It may involve either a reduced breakdown of AQP-CD, or an increased synthesis of it. The long-term regulation of AQP-CD expression may be an important factor in disorders associated with defects in urinary concentrating ability or with chronic alterations in circulating AVP levels such as nephrogenic and pituitary diabetes insipidus, compulsive water drinking, abnormally low potassium levels, and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In most of these disorders, there is a lag time between the correction of disorder and the correction with the lack of urinary concentration that accompanies it. This lag could be due in part to an up- or down-regulation of AVP sensitive water channels like AQP-CD.