Molecular and Cellular Biology of Vasopressin and Oxytocin Receptors and Action in the Kidney
| Title: | Molecular and Cellular Biology of Vasopressin and Oxytocin Receptors and Action in the Kidney |
|---|---|
| Author: | Bichet, Daniel G. |
| Publisher: | Current Opinion in Nephrology and Hypertension |
| Date Published: | January 01, 1994 |
| Reference Number: | 112 |
The molecular cloning and characterization of receptors for [Arg8] vasopressin and oxytocin were recently accomplished. These receptors form a subfamily among the large number of quanine nucleotide-binding regulatory protein (G protein)-coupled receptors with seven transmembrane domains. The molecular cloning of the human V2 receptor was rapidly followed by the identification of mutations in the V2 receptor gene segregating with the clinical phenotype in families with X-linked nephrogenic diabetes insipidus. These naturally occurring mutations will be useful to identify critical functional regions of the vasopressin V2 receptor. Carrier detection and early diagnosis of affected male infants are available and can avert the physical and mental retardation that are the consequences of episodes of dehydration. Together with the recent cloning of the vasopressin-regulated water channels in the apical membrane of the collecting tubule, these developments will enable direct investigation of the mammalian concentrating mechanism.
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)
- helping to inhibit excessive urination,
- aiding smooth muscles to contract,
- helping to regulate body temperature and blood pressure,
- stimulating certain liver processes,
- regulating the release of adrenocorticotropin hormone,
- and helping platelets (tiny, disc-shaped structures in the blood that help with coagulation) come together.
A receptor is a molecular structure that binds with a hormone such as AVP, thus initiating a specific molecular sequence that results in a bodily function. G-protein coupled receptors are a family of receptors with a common shape. They are located within specific cell membranes, the thin strip that encircles each cell, separating the inside from the outside of the cell. If you imagine the G-protein coupled receptor as a beaded string, most of it lies in seven folded clumps (called the seven transmembrane domains) inside the cell membrane. Part of the receptor snakes outside the membrane into the outside of the cell forming three curves called extracellular loops 1, 2 and 3. Part of it snakes inside the cell forming three curves called intracellular loops 1, 2 and 3. One end of the receptor, called the amino-terminus, lies outside the cell with the extracellular loops. The other end, called the carboxy-terminus, lies inside the cell with the intracellular loops. (Look at a diagram of a G-protein coupled receptor.)
It is thought that the columns of the transmembrane helices interact with each other to form a pocket where the hormone that it is specific to the helices can bind. When the binding occurs, the shapes of the receptor and hormone change to enable them to activate the G-protein to which it is coupled so the molecular sequence initiated by the binding can continue.
The vasopressin-2 receptor (V2R) is the G-protein coupled receptor to which AVP binds to affect urine concentration and water reabsorption on the part of the kidney. When the V2R is unable to bind with AVP due to some deformation caused by a mutation of the V2R gene that forms it, then the kidney cannot concentrate urine or reabsorb water. This disorder is called nephrogenic diabetes insipidus (NDI).
Researchers worldwide have located different mutations and their locations on the V2R gene. They also have determined the inheritance pattern of NDI caused by mutant V2R. This pattern is an X-linked recessive pattern in which females can carry a mutant V2R gene but do not express NDI symptoms strongly or at all, whereas the males who inherit the mutant genes do express NDI symptoms. It is now possible to perform prenatal testing or immediate postnatal testing in families with a history or with likely histories of X-linked NDI. The early testing can prepare parents and medical personnel to appropriately treat for NDI in a timely manner, thus averting the possible physical and mental retardation that could arise from NDI-caused dehydration in an infant.