Regulation of Collecting Duct Water Permeability Independent of cAMP-Mediated AVP Response
| Title: | Regulation of Collecting Duct Water Permeability Independent of cAMP-Mediated AVP Response |
|---|---|
| Authors: | Lankford, Scott P.; Chou, Chung-Lin; Terada, Yoshio; Wall, Susan M.; Wade, James B.; Knepper, Mark |
| Publisher: | American Journal of Physiology |
| Date Published: | September 01, 1991 |
| Reference Number: | 357 |
We have used the isolated perfused tubule technique, measurements of adenosine 3',5'-cyclic monophosphate (cAMP) content in single tubules, and freeze-fracture electron microscopy to study the basis of high vasopressin-independent (basal) osmotic water permeability (Pf) in the terminal inner medullary collecting duct (IMCD) of the rat. The results confirmed the observation that the basal Pf of the terminal IMCD is considerably higher than that of the initial IMCD. They also showed that the basal Pf of the terminal IMCD is regulated by in vivo factors related to water intake, such that a very high vasopressin-independent Pf can be induced in isolated tubules by prior in vivo thirsting. Tubules from thirsted rats did not display elevated urea permeabilities, nor did they exhibit measurable cAMP levels in the absence of exogenous vasopressin, indicating that the high basal Pf was not due to residual binding of vasopressin to its receptors. Freeze-fracture studies in thirsted rats demonstrated the presence of intramembrane particle (IMP) clusters in both initial and terminal IMCD, with more in the latter. Water loading of the rats suppressed the incidence of clusters almost entirely but did not fully suppress the basal Pf in the terminal IMCD, raising the possibility that a component of transepithelial water transport may occur independently of the vasopressin-regulated IMP clusters. On the basis of these results, we conclude that the vasopressin-independent Pf in the terminal IMCD can be stably elevated to very high levels in response to in vivo thirsting. This elevation appears to be due to a chronic conditioning effect mediated by unknown in vivo factors and is not due to the short-term cAMP-mediated regulatory effect of vasopressin.
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.
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Their functional differences refer to their respective degrees of water permeability (Pf) and urea permeability (Purea), both in the presence and in the absence of the antidiuretic hormone, vasopressin (VP). In this instance, permeability refers to the degree to which the apical membranes in the cells of both IMCD sections allow urea and water to pass through them. These varying degrees of permeability are essential for the urine concentrating process. The Purea of the terminal IMCD is regulated by VP, not so the initial IMCD. Pf, when VP is not present, is higher in the terminal than the initial IMCD. Lankford, et al., report on their work to determine the basis of the high VP-independent Pf in the terminal IMCD.
To accomplish their work, the authors worked with rat IMCD tissue, measuring its Pf and Purea, cyclic adenosine monophosphate (cAMP) levels, and observing structural differences in the cells that comprised the tissue through freeze-fracture electron microscopy. They found that:
- VP increases the Pf of both segments of the IMCD. In the presence of VP, the Pf in the terminal IMCD was substantially higher than in the initial IMCD. In the absence of VP, the Pf of the terminal IMCD was still extremely high (higher than the Pf of the initial IMCD even in the presence of VP).
- In rats that were restricted from water while alive, the Pf can be increased to a very high level even without VP.
- The VP-induced increase in Pf in the terminal IMCD is mediated by elevated cAMP levels. That is, cAMP is an important part of the molecular sequence initiated by VP that leads to urine concentration. cAMP also mediates Purea increases in the terminal IMCD.
- Electron microscopy revealed that the IMCD tissue of rats restricted from water had more intramembrane particle (IMP) clusters in both segments of the IMCD, with more in the terminal segment. (IMPs are associated with increases in Pf.) Whereas the IMCD tissue of rats who had ample water while alive showed almost no IMP clusters. Still, the Pf of the terminal IMCD of these water-loaded rats was still sufficiently high to allow a substantial flow of water across the apical membrane, even in the absence of VP.
The most important conclusion the authors drew from their study was that the Pf of the terminal IMCD can be regulated by a process that is independent of VP-regulated IMP clusters. VP increases Pf by initiating an increase in the level of cAMP, which results in an increase of IMP clusters that increase the Pf of the apical membranes of the cells in the IMCD segments. Lankford, et al., discovered the possibility that the Pf may also be regulated by a process independent of VP; an as yet unknown regulatory process initiated by restricting rats from water for 24 hours.