downregulation

The definitions used in this glossary of terminology either have been provided by the authors of the articles, or have been extracted wholly or in part, or paraphrased from the following sources: The American Medical Association Encyclopedia of Medicine, Charles B. Clayman, MD, Medical Editor, Random House, New York, 1989; Biotechnology from A to Z, 2d Edition, William Bains, Oxford University Press, New York, New York, 2002; A Dictionary of Genetics, 6th Edition, Robert C. King and William D. Stansfield, Oxford University Press, New York, New York, 2002; Dorland's Illustrated Medical Dictionary, 29th and 30th Editions, W. B. Saunders Company, Philadelphia, 2000, 2003; Genes VII, Benjamin Lewin, Oxford University Press, New York, New York, 2000; The Gale Encyclopedia of Genetic Disorders, Volumes I and II, Stacey L. Blachford, Ed., Thomson Learning, New York, New York, 2002; The Merriam-Webster Dictionary, Merriam-Webster, Inc., Springfield, Massachusetts, 1997; Molecular Biology of the Cell, 3rd Edition, Bruce Alberts, et al., Garland Publishing, 1994; The Random House Dictionary of the English Language, Unabridged Edition, 1966; Webster's Ninth New Collegiate Dictionary, 1991.

DEFINITION:

downregulation
A decrease in the number of receptors for a chemical or drug on cell surfaces in a given area, usually due to long-term exposure to the agent. (Dorland's Illustrated Medical Dictionary, 29th edition)


Downregulation of aquaporin 2: The number of aquaporin 2 water channels will be decreased, i.e., regulated to a lower number of channels expressed on the luminal membrane (D. Bichet).


Downregulation of AQP2 means that there are many conditions with acquired nephrogenic diabetes insipidus (vasopressin-resistent polyuria) which result in a reduction in the levels of AQP2 protein in the collecting duct cells. Since AQP2 is essential for reabsorption of water from the collecting duct lumen back to the circulation, the absence or reduced levels of AQP2 (downregulation) results in the development of polyuria. Thus the conditions associated with this downregulation of AQP2 share many common features with the inherited forms of NDI (with mutations in vasopressin V2 receptor) since this condition is also associated with a reduced/absence of regulation of AQP2. This regulation is important for keeping the levels of AQP2 protein up, but it is also extremely important in regulating the trafficking of AQP2 from the reservoir in small vesicles to the apical plasma membrane (its active site for water reabsorption—the site where the water channel faces the water to be reabsorbed). This is why the studies of the very common acquired forms of NDI are very important in connection with inherited NDI (the shared elements of regulation or rather dysregulation) (S. Nielsen).

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