Water Channels and Urea Transporters
| Title: | Water Channels and Urea Transporters |
|---|---|
| Author: | Wintour, E. Marelyn |
| Publisher: | Clinical and Experimental Pharmacology and Physiology |
| Date Published: | January 01, 1997 |
| Reference Number: | 3 |
1. It now appears that when water crosses an endothelium which is not fenestrated, or an epithelium with tight junctions, it does so rapidly, and with low energy cost, only if the cell membrane contains an adequate number of specific water channels, encoded by one of at least six different genes.
2. The water channel genes so far cloned encode a series of integral membrane proteins called aquaporins, all of approximately 30 kDa (265-282 amino acids), in the unglycosylated state. All but one (AQP3) are specific water channels and all but one (AQP4) are inactivated by mercurial compounds.
3. Aquaporin 0 is the major (60%) intrinsic protein (mip) of lens fibre cells of the eye. Mutations in this gene are associated with cataract formation in mice.
4. Aquaporin 1, also called CHIP-28, exists in the membrane as a homotetramer, and is present in red blood cells, the choroid plexus, the proximal tubule and descending limb of the loop of Henle in the kidney as well as in many other sites. Surprisingly, no pathological consequence is known in patients lacking a functional AQP1 gene.
5. Aquaporin 2, also called WCH-CD, is the water channel of the principal cell of the cortical and medullary collecting duct, and is located in cytoplasmic vesicles unless arginine vasopressin is acting, when it is translocated to the apical membrane by synaptobrevins or vesicle associated membrane protein 2 (VAMP2). Lack of functional AQP2 gene leads to a rare form of nephrogenic diabetes insipidus.
6. Aquaporins 3, 4, and 5 are located in many tissues - AQP3 and AQP4 being in the basolateral membrane of the renal cortical and medullary principal cell, as well as in the gastrointestinal tract (AQP3) and the brain (AQP4).
7. Four sequences are known for urea transporters HUT11 - the urea transporter of the human red cell membrane, and HUT2, rUT2, rbUT2 - the arginine vasopressin inducible urea transporters of the human, rat and rabbit kidney. They are specifically permeable to urea, not to water, and are claimed to be inhibited by phloretin.
8. The water channel proteins contain six membrane-spanning regions, whilst the urea transporters are thought to contain at least 10 membrane spanning segments.
9. Very little work has examined the ontogeny of these proteins, except in the rat, and virtually nothing is known of the expression of these genes in pregnancy or in any disorder of fluid balance in the mother or fetus.
2. The water channel genes so far cloned encode a series of integral membrane proteins called aquaporins, all of approximately 30 kDa (265-282 amino acids), in the unglycosylated state. All but one (AQP3) are specific water channels and all but one (AQP4) are inactivated by mercurial compounds.
3. Aquaporin 0 is the major (60%) intrinsic protein (mip) of lens fibre cells of the eye. Mutations in this gene are associated with cataract formation in mice.
4. Aquaporin 1, also called CHIP-28, exists in the membrane as a homotetramer, and is present in red blood cells, the choroid plexus, the proximal tubule and descending limb of the loop of Henle in the kidney as well as in many other sites. Surprisingly, no pathological consequence is known in patients lacking a functional AQP1 gene.
5. Aquaporin 2, also called WCH-CD, is the water channel of the principal cell of the cortical and medullary collecting duct, and is located in cytoplasmic vesicles unless arginine vasopressin is acting, when it is translocated to the apical membrane by synaptobrevins or vesicle associated membrane protein 2 (VAMP2). Lack of functional AQP2 gene leads to a rare form of nephrogenic diabetes insipidus.
6. Aquaporins 3, 4, and 5 are located in many tissues - AQP3 and AQP4 being in the basolateral membrane of the renal cortical and medullary principal cell, as well as in the gastrointestinal tract (AQP3) and the brain (AQP4).
7. Four sequences are known for urea transporters HUT11 - the urea transporter of the human red cell membrane, and HUT2, rUT2, rbUT2 - the arginine vasopressin inducible urea transporters of the human, rat and rabbit kidney. They are specifically permeable to urea, not to water, and are claimed to be inhibited by phloretin.
8. The water channel proteins contain six membrane-spanning regions, whilst the urea transporters are thought to contain at least 10 membrane spanning segments.
9. Very little work has examined the ontogeny of these proteins, except in the rat, and virtually nothing is known of the expression of these genes in pregnancy or in any disorder of fluid balance in the mother or fetus.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
For many years it has been known that water and urea (waste from the breakdown of proteins) freely pass in and out of red cell membranes. Recently two important discoveries have been made regarding this phenomenon. Researchers now understand the molecular basis for this occurrence, and they now know that red cell membranes are not typical of all cell membranes.
Anywhere that fluid is secreted, it quickly and easily crosses epithelial barriers. Water is part of this fluid. It seems to flow quickly through the body because of water channels in the cell membranes. These various water channels are all called aquaporins (AQP).
In addition to containing aquaporins, red cell membranes also contain urea transporters. Urea enters cells through urea transporters and water enters cells through water channels. Even though water molecules are smaller than urea molecules, water molecules do not pass through urea transporters. To date, only two specific urea transporters have been found: one is found in the renal medulla (in the kidney) and is inducible by ADH or AVP; the other is non-AVP induced. (The author does not mention where it is found.)
Urea transporters are needed in the kidneys to conserve water when blood is too concentrated. To conserve this water, the kidneys need to flush out urea without flushing water at the same time.
Water channels are equally important. Water flows in and out of cells throughout the body except in some places in the kidneys. Cells shrink in hypotonic environments (places where there is too little water) and swell in hypertonic environments (places where there is too much water). Ideally fluid inside the cells (intracellular fluid--ICF) should be the same tonicity (contain the same concentration of water) as fluid outside the cells (extracellular fluid--ECF). To regulate this balance, some cells \"sense\" the concentration of water outside of them and send out the appropriate amount of antidiuretic hormone (ADH) or arginine vasopressin (AVP) to keep the correct amount of water in the blood. The AVP initiates a series of actions which results in water channel proteins being sent to cells which need more water. Once the water channel proteins are in place, the cell absorbs the water it needs. When the correct balance between ECF and ICF has been restored, the water channel proteins are removed from the cell membrane.
Descriptions of Aquaporins
AQP1 Also known as CHIP-28, it is the most ubiquitous of all the aquaporins. It is the major water channel of the red blood cells. In the kidneys it is involved in the reabsorption of most of the waste filtered through the glomeruli. Some cells in rats contain 20 million AQP1; some humans have none, but there appears to be no physical effect.
AQP2 This water channel makes principal cells of the inner medullary collecting duct in the kidneys more permeable to water. When a mutant AQP2 is nonfunctional, nephrogenic diabetes insipidus occurs in the person.
AQP3 This is the only water channel which allows anything but water to pass through its channel; urea and glycerol use it as well.
With the advent of so much increased knowledge about water channels and urea transporters, developmental physiologists have new tools with which to answer some intriguing questions.