Biomaterial Database

Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus. 2010

E L Los, and P M T Deen, and J H Robben

Department of physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

According to the body's need, water is reabsorbed from the pro-urine that is formed by ultrafiltration in the kidney. This process is regulated by the antidiuretic hormone arginine-vasopressin (AVP), which binds to its type 2 receptor (V2R) in the kidney. Mutations in the gene encoding the V2R often lead to the X-linked inheritable form of nephrogenic diabetes insipidus (NDI), a disorder in which patients are unable to concentrate their urine despite the presence of AVP. Many of these mutations are missense mutations that do not interfere with the intrinsic functionality of V2R, but cause its retention in the endoplasmic reticulum (ER), making it unavailable for AVP binding. Because the current treatments for NDI relieve its symptoms to some extent, but do not cure the disorder, cell-permeable antagonists (pharmacological chaperones) have been successfully used to stabilise the mutant receptors and restore their plasma membrane localisation. Recently, cell-permeable agonists also were shown to rescue ER-retained V2R mutants, leading to increased cAMP levels and translocation of aquaporin-2 to the apical membrane. This makes V2R-specific cell-permeable agonists very promising therapeutics for NDI as a result of misfolded V2R receptors.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D002463	Cell Membrane Permeability	A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.	Permeability, Cell Membrane
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017483	Receptors, Vasopressin	Specific molecular sites or proteins on or in cells to which VASOPRESSINS bind or interact in order to modify the function of the cells. Two types of vasopressin receptor exist, the V1 receptor in the vascular smooth muscle and the V2 receptor in the kidneys. The V1 receptor can be subdivided into V1a and V1b (formerly V3) receptors.	Antidiuretic Hormone Receptors,Receptors, V1,Receptors, V2,V1 Receptors,V2 Receptors,Vasopressin Receptors,8-Arg-Vasopressin Receptor,Antidiuretic Hormone Receptor,Antidiuretic Hormone Receptor 1a,Antidiuretic Hormone Receptor 1b,Arginine Vasopressin Receptor,Argipressin Receptor,Argipressin Receptors,Receptor, Arginine(8)-Vasopressin,Renal-Type Arginine Vasopressin Receptor,V1 Receptor,V1a Vasopressin Receptor,V1b Vasopressin Receptor,V2 Receptor,Vascular-Hepatic Type Arginine Vasopressin Receptor,Vasopressin Receptor,Vasopressin Receptor 1,Vasopressin Type 1A Receptor,Vasopressin V1a Receptor,Vasopressin V1b Receptor,Vasopressin V2 Receptor,Vasopressin V3 Receptor,8 Arg Vasopressin Receptor,Hormone Receptor, Antidiuretic,Hormone Receptors, Antidiuretic,Receptor, Antidiuretic Hormone,Receptor, Arginine Vasopressin,Receptor, Argipressin,Receptor, V1,Receptor, V2,Receptor, Vasopressin,Receptor, Vasopressin V1b,Receptor, Vasopressin V3,Receptors, Antidiuretic Hormone,Receptors, Argipressin,Renal Type Arginine Vasopressin Receptor,V1b Receptor, Vasopressin,Vascular Hepatic Type Arginine Vasopressin Receptor,Vasopressin Receptor, V1b
D018500	Diabetes Insipidus, Nephrogenic	A genetic or acquired polyuric disorder characterized by persistent hypotonic urine and HYPOKALEMIA. This condition is due to renal tubular insensitivity to VASOPRESSIN and failure to reduce urine volume. It may be the result of mutations of genes encoding VASOPRESSIN RECEPTORS or AQUAPORIN-2; KIDNEY DISEASES; adverse drug effects; or complications from PREGNANCY.	ADH-Resistant Diabetes Insipidus,Acquired Nephrogenic Diabetes Insipidus,Congenital Nephrogenic Diabetes Insipidus,Diabetes Insipidus Renalis,Diabetes Insipidus, Nephrogenic, Autosomal,Diabetes Insipidus, Nephrogenic, Type 1,Diabetes Insipidus, Nephrogenic, Type I,Diabetes Insipidus, Nephrogenic, Type II,Diabetes Insipidus, Nephrogenic, X-Linked,Nephrogenic Diabetes Insipidus,Nephrogenic Diabetes Insipidus, Type I,Nephrogenic Diabetes Insipidus, Type II,Vasopressin-Resistant Diabetes Insipidus
D040181	Genetic Diseases, X-Linked	Genetic diseases that are linked to gene mutations on the X CHROMOSOME in humans (X CHROMOSOME, HUMAN) or the X CHROMOSOME in other species. Included here are animal models of human X-linked diseases.	X-Linked Genetic Diseases,Genetic Diseases, X-Chromosome Linked,Disease, X-Linked Genetic,Diseases, X-Linked Genetic,Genetic Disease, X-Linked,Genetic Diseases, X Chromosome Linked,Genetic Diseases, X Linked,X Linked Genetic Diseases,X-Linked Genetic Disease
D065092	Antidiuretic Hormone Receptor Antagonists	Endogenous compounds and drugs that inhibit or block the activity of ANTIDUIRETIC HORMONE RECEPTORS.	Antidiuretic Hormone Antagonist,Antidiuretic Hormone Receptor Antagonist,Vasopressin Antagonist,Vasopressin Receptor Antagonist,Antidiuretic Hormone Antagonists,Vasopressin Antagonists,Vasopressin Receptor Antagonists,Antagonist, Antidiuretic Hormone,Antagonist, Vasopressin,Antagonist, Vasopressin Receptor,Antagonists, Antidiuretic Hormone,Antagonists, Vasopressin,Antagonists, Vasopressin Receptor,Hormone Antagonist, Antidiuretic,Hormone Antagonists, Antidiuretic,Receptor Antagonist, Vasopressin,Receptor Antagonists, Vasopressin

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