Aquaporin channels appear in simulations to allow only water to pass, as the molecules effectively queue up in single file. Aug, 2004 ewa tomkowiak and joanna romana pienkowska, the current knowledge of invertebrate aquaporin water channels with particular emphasis on insect aqps, advances in cell biology, 10. Transcellular water movement can be mediated by the transmembrane protein family of aqps aquaporins, as has also been recently identi. Aquaporin water channels peter agre roderick mackinnon all living matter is made up of cells. Recent studies suggest that several aquaporin proteins are present in the mammary gland. Role of aquaporin water channels in airway fluid transport. Structure and function of aquaporin water channels. Generation and phenotype of a transgenic knockout mouse lacking the mercurialinsensitive water channel aquaporin4. May 29, 2001 the goal of this study was to define the role of aquaporin water channels in airway physiology. The exocrine pancreas secretes large volumes of isotonic fluid, most of which originates from the ductal system.
New insights into aquaporin evolution and physiology in. Like the kidney, the intestine can also contribute to water homeostasis maintenance by modulating water and electrolytes absorption and. Aug 18, 2005 recent data suggest that canalicular bile secretion involves selective expression and coordinated regulation of aquaporins aqps, a family of water channels proteins. Water channel aquaporin 8 is a critical regulator of. Colon water transport in transgenic mice lacking aquaporin4. The transcellular water movement is tightly controlled by the amount and activity of water channels, known as aquaporins, present in cellular membranes. However, although membrane water channels were predicted to exist as early as the 1970s, it was not until 1992 that the first aquaporin water channel was serendipitously discovered by peter agre and collaborators preston et al. Of the human isoforms, eight aqps have been detected.
Not surprisingly, water transport is a major process in kidney physiology. Role of aquaporin water channels in kidney and lung. Department of medicine, division of pulmonary and critical care medicine, johns hopkins university school of medicine, baltimore, maryland 21205. Aquaporin aqp water channels provide the molecular pathway for cell membrane water transport in many cell types.
Stomach and intestines are involved in the secretion of gastrointestinal. Several aquaporins a family of integral membrane proteins have been recently identified in the mammalian gastrointestinal tract, and their involvement in the movement of fluid and small solutes has been suggested. In addition to water and glycerol, there is evidence, some of which is controversial, that some aquaporins pass gases co 2, nh 3, no, o 2, various small solutes such as h 2o 2 and. This is done by changing aquaporin density and activity in the membrane, including posttranslational modifications and protein interaction that act on their. Expression and immunolocalization of the aquaporin8 water channel in rat gastrointestinal tract. The phenotype analysis of transgenic mice deficient in specific aquaporin water channels has provided new insights into the role of aquaporins in organ physiology. Aquaporin6 is expressed along the rat gastrointestinal tract. New perspectives on the potential role of aquaporins aqps.
Aquaporin water channels and lung physiology american. However, water is frequently overlooked as a nutrient. Aquaporin water channels in gastrointestinal physiology core. Jun 01, 1999 the aquaporin family of molecular water channels. Distribution of aquaporins and sodium transporters in the. Calamita g, mazzone a, bizzoca a, cavalier a, cassano g, thomas d, svelto m. Aquaporin water channels in gastrointestinal physiology.
In order to directly compare the results of md simulations with biochemical measurements of the conductivity of membrane water channels, in which osmotic pressure gradients are used to induce the flow of water across the membrane, we developed a new methodology for md simulations. Aquaporin water channels nobel lecture, december 8, 2003 by peter agre the johns hopkins university school of medicine, baltimore, md 21205, usa. The gastrointestinal tract is the major organ for water transport and is only secondary to kidneys. Until now, at least 11 aqps aqp111 have been found to be present in the stomach, small and large intestines. Aquaporin aqp water channels are expressed in highgrade tumor cells of different tissue origins, without known function. The paradox was solved by the discovery of a family of 28 kda membrane transporters with high permeability for water 10. Functional characterization of the first aquaporin membrane protein was reported in 1992, but most membrane physiologists felt that there must be openings pores or channels in cell membranes to permit a flow of water, because the osmotic permeability of some epithelial cells was much too large to be accounted for by simple diffusion through the plasma membrane. The water molecule flips when interacting with both asparagines of the npa motifs, and moves further down the channel with the oxygen facing upwards fig.
Aquaporins are found in most living organisms, in which they are involved in many different physiological processes gomes et al. Molecular biology and physiology of water and solute transport. Aquaporin water channels in gastrointestinal physiology aquaporin water channels in gastrointestinal physiology ma, tonghui. Transcellular water flux, including in the intestinal mucosa, primarily occurs via aquaporin aqp family water channels. The goal of this study was to define the role of aquaporin water channels in airway physiology. Recent data suggest that canalicular bile secretion involves selective expression and coordinated regulation of aquaporins aqps, a family of water channels proteins. Guided by the aquaporin s local electric field, the oxygen in each water molecule faces forwards as it enters, turning around half way along and leaving with the oxygen facing backwards. Distribution of aquaporin water channels aqp1 and aqp5 in. Aquaporin aqp water channels, first discovered in 1991, 3, 4 are known to enhance the water permeabilities of a wide range of epithelia. Aquaporin water channels in kidney peter agre departments of biological chemistry and medicine, johns hopkins school of medicine, baltimore, maryland.
Increased migration and metastatic potential of tumor cells. Extensive data indicate that aqps, working as water channel proteins. Aquaporin 1 was the first specific water channel to be characterized in red blood cells preston and agre, 1991. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. Distribution of aquaporin water channels aqp1 and aqp5 in the. Guided by the aquaporins local electric field, the oxygen in each water molecule faces forwards as it enters, turning around half way along and leaving with the oxygen facing backwards. As a first year medical student, i attended nearly 200 lectures, but i have clear recollections of only two. Request pdf aquaporin water channels in gastrointestinal physiology fluid transport is a major function of the gastrointestinal gi tract with more than 9 litres of fluid being absorbed or. Wang ks, ma t, filiz f, verkman a, bastidas ja 2000 colon water transport in transgenic mice lacking aquaporin4 water channels. We studied a set of airway functions that were postulated to require aquaporins, including humidification in upper and lower airways, hydration of the airway surface liquid, and fluid absorption by upper airways.
Mammalian aquaporins aqps are transmembrane channels expressed in a large variety of cells and tissues throughout the body. Aquaporin 2 is in kidney epithelial cells and usually lies dormant in intracellular vesicle membranes. Aquaporin water channels aqps represent a major transcellular route for water transport in the gastrointestinal tract. Generation and phenotype of a transgenic knockout mouse lacking the mercurialinsensitive water channel aquaporin 4. The paradox was solved by the discovery of a family of 28 kda. This fast transepithelial fluid transport occurs either via transcellular pathways, which are mediated by passive diffusion, aquaporin aqp water channels 2,3 and cotransporters 4,5, or via paracellular pathways by tight junctions, or both 6,7. Immunolocalization of aquaporin10 in tuberculous human. Aqp12, have been identified in mammals, which regulate various important biological. Nine aquaporintype water channels have been identified in mammalian tissues aqp1aqp9 and many more in plants and lower organisms. This description is written from the perspective of water entering a cell through an aquaporin. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. In order to further characterize the role of aqps in this process, an in vitro cell system with retained polarity and expression of aqps and relevant solute transporters involved in bile formation is highly desirable. A single human being has as many as the stars in a galaxy, about one hundred thousand million.
Water diffusion across cell membranes is facilitated by aquaporins that provide plants with the means to rapidly and reversibly modify water permeability. In this direction we investigated, in some regions of the rat gastrointestinal tract, the presence and localization of aquaporin 6, given its peculiar function as an ion selective. Aquaporins aqps are emerging, in the last few decades, as critical proteins regulating water fluid homeostasis in cells involved in inflammation. However, the amount of aquaporin protein expression in hepatocytes has not been determined, nor is there. Aquaporins are membrane proteins that play fundamental roles in water and small solute transport across epithelial and endothelial barriers. Aquaporin water channels the fact that water has the ability to cross the hydrophobic membrane and enter and leave cells had been known for decades,but the mechanism wassomewhatofa paradox.
Fluid transport is a major function of the gastrointestinal gi tract with more than 9 litres of fluid being absorbed or secreted across epithelia in human salivary gland, stomach, the hepatobiliary tract, pancreas, small intestine and colon. The aquaporins are small integral membrane proteins whose six. The gastrointestinal tract moves a large amount of fluid, quantitatively second only to that of the kidney. To date, different aqps, encoded by the genes aqp0aqp12, have been identified in mammals, which regulate various important biological. Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions.
We studied a set of airway functions that were postulated to require aquaporins, including humidification in upper and lower airways, hydration of the airway surface liquid, and. The aqps are a family of small, integral membrane proteins that transport water and, in some cases, water and small solutes. In man, about 9 lday of water deriving from diet and digestive juices are absorbed, and about 12 lday are secreted with enteric juice. Expression and subcellular localization of aquaporin water. Dec, 20 aquaporins are membrane proteins that play fundamental roles in water and small solute transport across epithelial and endothelial barriers. In the gastrointestinal tract of mammals, water can either be secreted with digestive juices or absorbedby the small and large intestine.
The aquaporin family aquaporin subtypes and classification as previously mentioned, the aquaporins are a growing family of molecular water channels, first identified in the early 1990s. Verkman, in physiology of the gastrointestinal tract fourth edition, 2006. S lessons on renal physiology from transgenic mice lacking aquaporin water channels. Structure and function of aquaporin water channels american. An update on physiology and pathophysiology of aquaporin2. Aquaporin water channels in gastrointestinal physiology ma. Expression, distribution and role of aquaporin water channels. If the flow of water through the channel is accompanied by ions without selection, the conductivity in a 100 mm salt is expected to be 0.
Aqps represent a family of ubiquitous membrane channels that regulate osmotically water flux in various tissues and sometimes the transport of small solutes, including glycerol. Plant growth and development are dependent on tight regulation of water movement. We hypothesized that aqps in tumor cells may facilitate their migration and thus their metastatic potential, which, if correct, would suggest aqp inhibition as a possible strategy for inhibition of tumor spread. Immunohistochemical techniques have confirmed the presence of aquaporin 1 aqp1 and aqp3 water channels in rat, mouse, bovine and human mammary. The oxygen faces down when the water molecule enters from the extracellular side. Aquaporin channels in the heartphysiology and pathophysiology. Aqp1deficient mice are polyuric and are unable to concentrate their urine in response to water deprivation or vasopressin administration. Aquaporin water channels in gastrointestinal physiology, the. Defective secretion of saliva in transgenic mice lacking aquaporin5 water channels. Boron, mutation of a single amino acid converts the human water channel aquaporin 5 into an anion channel, american journal of physiologycell physiology, 305, 6, c663, 20. Aquaporin4 water channels in enteric neurons europe pmc. Aquaporin6 is expressed along the rat gastrointestinal. Expression, distribution and role of aquaporin water. When it is needed, vasopressin binds to the cell surface vasopressin receptor thereby activating a signaling pathway that causes the aquaporin 2 containing vesicles to fuse with the plasma membrane, so the aquaporin 2 can be used by the cell.
Expression and localisation of known aqp isoforms was examined in normal human pancreas, pancreatic adenocarcinoma, and pancreatic cell lines of ductal origin capan1, capan2. The longstanding problem of membrane water transport has been advanced by the recognition of a new family of water transport proteins, the aquaporins. Immunohistochemical techniques have confirmed the presence of aquaporin 1 aqp1 and aqp3 water channels in rat, mouse, bovine and human mammary glands. Pathophysiology of the aquaporin water channels annual.
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