Aquaporin mediated water flux as a target for diuretic development.
Within the past decade an entire family of membrane proteins--aquaporins--which function as transmembrane water channels has been identified; they occur throughout the plant, animal, and bacterial kingdoms. Several family members permit glycerol and urea permeability. Most aquaporins are inhibited by mercury. Constitutively expressed aquaporin 1 is the major permeability channel of the proximal tubule, descending thin limb of the loop of Henle, and it is also found in vasa recta. Aquaporin 2 is expressed in the principal cells of the collecting duct where it shuttles between intracellular vesicles and the apical membrane in response to vasopressin. Aquaporin 2 mutations cause nephrogenic diabetes insipidus; increased aquaporin 2 activity is implicated in the pathophysiology of heart failure, cirrhosis, and nephrotic syndrome. Aquaporins 3 and 4 provide basolateral membrane water channels in the collecting duct. These 4 channels and 6 others are also found elsewhere throughout the body. The physiological importance of several of the channels remains unknown. Aquaporin 1 inhibitors might induce useful diuresis, but humans who lack aquaporin 1 have no significant clinical disease. Inhibition of aquaporin 2 activity by vasopressin receptor antagonists may be useful in heart failure, cirrhosis, nephrotic syndrome, and the syndrome of inappropriate antidiuretic hormone (ADH) release.
Laski
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ME
Combined Program in Nephrology and Renal Physiology, Texas Tech University Health Sciences Center, Lubbock, USA. medmel@ttuhsc.edu
Pressley
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TA
D000818:Animals; D020346:Aquaporins / Q000187:drug effects* / Q000378:metabolism*; D001692:Biological Transport; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D003920:Diabetes Mellitus / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D051379:Mice; D009404:Nephrotic Syndrome / Q000378:metabolism; D012680:Sensitivity and Specificity
D020346:Aquaporins; D004232:Diuretics