Molecular Cloning of the Receptor for Human Antidiuretic Hormone
|Title:||Molecular Cloning of the Receptor for Human Antidiuretic Hormone|
|Authors:||Birnbaumer, Mariel; Seibold, Anita; Gilbert, Stephanie; Ishido, Ph.D., Masami; Barberis, Claude; Antaramian, Anaid; Brabet, Philippe; Rosenthal, Walter|
|Date Published:||May 28, 1992|
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)
Birnbaumer, et al., report on their successful cloning of the gene which synthesizes one specific receptor that the antidiuretic hormone, arginine vasopressin (AVP) binds with. By binding with this specific receptor, which is located in the principal cells of the kidney collecting duct, AVP allows the kidneys to concentrate urine and reabsorb water flowing through the kidney collecting duct. The molecular sequence that allows the kidneys to do this is as follows: AVP binds with its receptor. This stimulates the enzyme, adenylyl cyclase. This elevates cAMP, and cAMP helps direct water-transporting proteins to insert themselves in the apex of the membranes of the collecting duct principal cells. This makes the membranes more water permeable. And this is what allows urine concentration and water reabsorption.
To clone the receptor gene, the authors first constructed a set of cloned DNA fragments. They screened the clones for their ability to be responsive to AVP. This was measured by the amount of AVP binding sites per cell. They also measured the clones that created cell responsiveness to AVP for their ability to affect cells in such a way as to stimulate adenylyl cyclase. Both these screenings indicate the presence in the clones of the AVP receptor.
Testing the degrees to which AVP and its analogs stimulated the cells containing the AVP receptor indicated that the AVP receptor was the vasopressin-2 receptor (V2R). The V2R is predicted to be 371 amino acids long with a relative molecular mass of 40,285. It is a member of the superfamily of G-protein-coupled receptors.