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- Title
Renal water reabsorption: A physiologic retrospective in a molecular era.
- Authors
Schafer, James A.
- Abstract
Renal water reabsorption: A physiologic retrospective in a molecular era. The cloning and sequencing of the aquaporin water channels has been an enormous advance in the biomedical sciences, as recognized by the award of the Nobel Prize to Peter Agre last year. Among many other examples, expression of aquaporin proteins inXenopusoocytes and other heterologous expression systems has confirmed two important models of renal function: the increase in the water permeability of the collecting duct by antidiuretic hormone (ADH), and the mechanism of near isosmotic volume reabsorption by the proximal tubule. These mechanisms were the subjects of intensive investigation by numerous investigators, including Thomas E. Andreoli, who is being honored by this symposium, and who developed many of the key concepts in these areas. His early work with artificial lipid bilayer membranes and the pore-forming antibiotic amphotericin provided the rigorous foundation in experimental and conceptual modeling techniques that he later applied to physiologic and pathophysiologic mechanisms in the kidney, which are summarized in this retrospective. Dr. Andreoli and his colleagues proposed a water channel mechanism for the action of ADH, which has been confirmed by the cloning and heterologous expression of aquaporin-2. They also proposed that volume reabsorption by the proximal tubule depended on a very high hydraulic conductivity and the development of luminal hypotonicity produced by active solute reabsorption. This model has also been confirmed in mice in which aquaporin-1 expression is knocked out, resulting in a low proximal tubule water permeability that exaggerates the development of luminal hypotonicity.
- Subjects
AQUAPORINS; WATER-electrolyte balance (Physiology); GLYCOPROTEINS; MEMBRANE proteins; KIDNEY physiology; NEPHROLOGY; INTERNAL medicine
- Publication
Kidney International Supplement, 2004, Issue 91, pS20
- ISSN
0098-6577
- Publication type
Article
- DOI
10.1111/j.1523-1755.2004.09104.x