Biomaterial Database

Pharmacological chaperones in nephrogenic diabetes insipidus: possibilities for clinical application. 2007

Joris H Robben, and Peter M T Deen

Molecular Pharmacology Group, Institute for Biomedical and Life Sciences, University of Glasgow, Glasgow, UK.

The antidiuretic hormone arginine-vasopressin regulates water homeostasis in the human body by binding to its vasopressin type 2 receptor (V2R). Mutations in AVPR2, the gene encoding V2R, lead to the X-linked congenital form of nephrogenic diabetes insipidus (NDI), a disease characterized by the inability to concentrate urine in response to vasopressin; often this involves missense mutations or deletion of one or a few amino acids. In vitro V2R expression studies revealed that the function of most of these receptors is not disturbed, but due to their misfolding, the quality control mechanism of the endoplasmic reticulum (ER) retains these receptors inside the cell, thereby preventing their functioning at the plasma membrane. This review summarizes our current knowledge on ER retention of V2R mutants, and describes the different approaches that have been undertaken to restore the plasma membrane expression and function of V2R mutants in NDI in vitro and in vivo. The use of cell permeable receptor ligands (called 'pharmacological chaperones') appears promising for the treatment of NDI in a subset of patients.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
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
D003545	Cysteine	A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.	Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D004721	Endoplasmic Reticulum	A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)	Ergastoplasm,Reticulum, Endoplasmic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
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
D017510	Protein Folding	Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.	Protein Folding, Globular,Folding, Globular Protein,Folding, Protein,Foldings, Globular Protein,Foldings, Protein,Globular Protein Folding,Globular Protein Foldings,Protein Foldings,Protein Foldings, Globular
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