Figure 40.10 ADH Induces Insertion of Aquaporins into Plasma Membranes
In 1993, Fushimi and colleagues cloned and characterized AQP-2, a water channel of the apical membrane of the kidney collecting duct cells. Shortly thereafter, a research group led by M. A. Knepper tested the hypothesis that ADH, or vasopressin, increases water permeability by inducing translocation of AQP-2 to the apical plasma membrane of the collecting duct cells. The researchers isolated collecting ducts from rat kidneys and used immunocytochemisty to visualize AQP-2 before, during, and after exposure to ADH. The ducts were also perfused with water to measure permeability of the duct cells to water. The results indicated that in the absence of ADH, AQP-2 was largely found in the plasma membrane of intracellular vesicles. By contrast, in the presence of ADH, AQP-2 localized to the apical plasma membrane of the collecting duct cells. After ADH washout, the AQP-2 was again found primarily in the membrane of intracellular vesicles. Together, these findings suggested that ADH increases the water permeability by stimulating insertion of AQP-2 into the plasma membrane of the collecting duct cells. In humans, mutations in the aquaporin-2 gene result in hereditary nephrogenic diabetes insipidus (NDI). As expected, based on the results above, this disorder is characterized by the inability of the kidney to concentrate urine in response to ADH. In addition to its role in the hereditary form of NDI, however, aquaporins are also involved in acquired forms of NDI. Specifically, acquired NDI can occur as a result of impaired regulation of aquaporin-2 due to administration of lithium salts, low blood potassium levels, high blood calcium levels, or chronically excessive water consumption beyond normal body needs. Patients with NDI are chronically thirsty and in danger of dehydration. Treatment of the disorder varies according to the form of NDI, but in all cases ready access to water is a must.
Original Papers
Fushimi, K., S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. 1993. Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature 361: 549–552.
http://dx.doi.org/10.1038/361549a0
Nielsen, S., C.-L. Chou, D. Marples, E. I. Christensen, B. K. Kishore, and M. A. Knepper. 1995. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of Aquaporin-CD water channels to plasma membrane. Proceedings of the National Academy of Sciences 92: 1013–1017.
http://www.pnas.org/cgi/reprint/92/4/1013.pdf
Links
Agre, P. 2006. The aquaporin water channels. Proceedings of the American Thoracic Society 3: 5–13.
http://www.atsjournals.org/doi/abs/10.1513/pats.200510-109JH#.VC1ncxbzLfV
Kimball’s Biology Pages: The Kidneys
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/K/Kidney.html
NCBI: Online Mendelian Inheritance in Man: Aquaporin 2
http://www.ncbi.nlm.nih.gov/omim/107777
Colorado State University: Hypertexts for Biomedical Sciences: Aquaporins: Water Channels
http://www.vivo.colostate.edu/hbooks/molecules/aquaporins.html
University of Illinois at Urbana-Champaign: Structure, Dynamics, and Function of Aquaporins
http://www.ks.uiuc.edu/Research/aquaporins/
Aquaporins.org
http://www.aquaporins.org/index.html