78 - Aquaporin Water Channels and the Endothelium

Summary

The aquaporins (AQPs) are a family of water transporting channels that are expressed in many mammalian tissues including epithelial, endothelial, and other cell types. At least ten AQPs are present in mammals, and more exist in amphibians, plants, and lower organisms. Functional measurements suggest that mammalian AQPs 1, 2, 4, 5, and 8 are primarily water-selective, whereas AQPs 3, 7, and 9 (called aquaglyceroporins) also transport glycerol and possibly other small solutes. The AQPs function as pores to increase water transport across cell membranes in response to an osmotic gradient. Structural studies of AQP1 indicate a tetrameric assembly in membranes in which each monomer contains six tilted helical segments surrounding a putative aqueous pore. Human mutations exist for several AQPs. Humans with mutations in AQP0, the major intrinsic protein of lens fiber (also called MIP) develop cataracts (1). Humans with mutations in the AQP1 gene (Colton blood group antigen) manifest a urinary concentrating defect (2), and humans with mutations in the AQP2 gene, the vasopressin-regulated water channel, have autosomal hereditary nephrogenic diabetes insipidus (3).

AQP1 is expressed strongly throughout microvascular endothelial beds outside the brain, such as in kidney (vasa recta), lung and airways, skin, secretory glands, skeletal muscle, pleura, and peritoneum (4,5). AQP1 also is expressed in the endothelium of proliferating tumor microvessels (6) and in nonvascular endothelial cells (ECs) in cornea, trabecular meshwork in the canal of Schlemm, and central lacteals in small intestine (4,5,7). Figure 78.1A shows immunolocalization of AQP1 in ECs in a variety of microvascular and nonvascular endothelia.