It has been known for several years that conditions such as chronic primary polydipsia, hypothyroidism, and adrenal disease are associated with abnormalities in urinary concentration and dilution. With the relatively recent discovery of aquaporin water channels and the development of techniques to assess the regulation and function of aquaporins and ion and urea transporters in the kidney, it is now possible to better understand the molecular mechanisms responsible for abnormal urinary concentration and dilution in these conditions. Therefore, the present studies are designed to first correlate alterations in the renal abundance of aquaporin water channels and ion and urea transporters with impaired urinary concentration and dilution in the above-named conditions. This will be accomplished using western immunoblotting techniques. Further investigation into the contributions of altered aquaporin-2 regulation and function to impaired urinary concentration and dilution in these conditions will be performed via a detailed assessment of vasopressin V2 receptor binding and affinity, western immunoblot of inner medulla Gs-alpha and adenylate cyclase abundance, measurement of cAMP production, and evaluation of AQP2 phosphorylation and trafficking. The results of these studies should give us a comprehensive understanding of the mechanisms that contribute to altered urinary concentration and dilution in chronic primary polydipsia, hypothyroidism, and adrenal disease. These results will provide a basis for translational studies addressing these concerns in patients affected by these disorders.
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