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Applications of aquaporin inhibitors.

The aquaporins are a family of small, integral membrane proteins that function as plasma membrane transporters of water and in some cases small polar solutes such as glycerol. There are at least 10 distinct aquaporins in mammals with specific patterns of expression in epithelial, endothelial and other tissues. Recent studies in aquaporin-null mice have indicated key roles for certain aquaporins in the urinary concentrating mechanism, fluid secretion by glands, brain swelling, skin moisture, hearing and vision, and gastrointestinal absorption. The only known inhibitors of some aquaporins are mercurial sulfhydryl-reactive compounds, which are too toxic and nonspecific for use in vivo. Small-molecule or peptide aquaporin blockers have potential applications in the treatment of disorders of fluid/pressure homeostasis such as heart failure, hypertension, brain swelling and glaucoma.