scholarly journals Functional Characterization of Vasopressin Type 2 Receptor Substitutions (R137H/C/L) Leading to Nephrogenic Diabetes Insipidus and Nephrogenic Syndrome of Inappropriate Antidiuresis: Implications for Treatments

2010 ◽  
Vol 77 (5) ◽  
pp. 836-845 ◽  
Author(s):  
Moulay D. Rochdi ◽  
Gabriel A. Vargas ◽  
Eric Carpentier ◽  
Geneviève Oligny-Longpré ◽  
Stanford Chen ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Functional Characterization ◽  
Inappropriate Antidiuresis

scholarly journals Characterization of five novel vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus reveals a role of tolvaptan for M272R-V2R mutation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Federica Prosperi ◽  
Yoko Suzumoto ◽  
Pierluigi Marzuillo ◽  
Vincenzo Costanzo ◽  
Sabina Jelen ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Functional Characterization ◽  
Urinary Concentration ◽  
Loss Of Function ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor

Abstract Nephrogenic diabetes insipidus (NDI) is a rare tubulopathy characterized by urinary concentration defect due to renal resistance to vasopressin. Loss-of-function mutations of vasopressin V2 receptor (V2R) gene (AVPR2) is the most common cause of the disease. We have identified five novel mutations L86P, R113Q, C192S, M272R, and W323_I324insR from NDI-affected patients. Functional characterization of these mutants revealed that R113Q and C192S were normally localized at the basolateral membrane of polarized Madin-Darby Canine Kidney (MDCK) cells and presented proper glycosylation maturation. On the other side, L86P, M272R, and W323_I324insR mutants were retained in endoplasmic reticulum and exhibited immature glycosylation and considerably reduced stability. All five mutants were resistant to administration of vasopressin analogues as evaluated by defective response in cAMP release. In order to rescue the function of the mutated V2R, we tested VX-809, sildenafil citrate, ibuprofen and tolvaptan in MDCK cells. Among these, tolvaptan was effective in rescuing the function of M272R mutation, by both allowing proper glycosylation maturation, membrane sorting and response to dDAVP. These results show an important proof of concept for the use of tolvaptan in patients affected by M272R mutation of V2R causing NDI.

scholarly journals Functional Characterization of the Molecular Defects Causing Nephrogenic Diabetes Insipidus in Eight Families1

2000 ◽  
Vol 85 (4) ◽  
pp. 1703-1710 ◽  
Author(s):  
Katharina Pasel ◽  
Angela Schulz ◽  
Kirsten Timmermann ◽  
Knut Linnemann ◽  
Maria Hoeltzenbein ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Functional Characterization ◽  
Molecular Defects

scholarly journals Functional characterization of AVPR2 mutants found in Turkish patients with nephrogenic diabetes insipidus

2018 ◽  
Vol 7 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Beril Erdem ◽  
Angela Schulz ◽  
Emel Saglar ◽  
Ferhat Deniz ◽  
Torsten Schöneberg ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Functional Characterization ◽  
Blood Stream ◽  
Receptor Activation ◽  
Receptor Function ◽  
Principal Cells ◽  
Genetically Determined ◽  
Turkish Patients

Diabetes insipidus is a rare disorder characterized by an impairment in water balance because of the inability to concentrate urine. While central diabetes insipidus is caused by mutations in the AVP, the reason for genetically determined nephrogenic diabetes insipidus can be mutations in AQP2 or AVPR2. After release of AVP from posterior pituitary into blood stream, it binds to AVPR2, which is one of the receptors for AVP and is mainly expressed in principal cells of collecting ducts of kidney. Receptor activation increases cAMP levels in principal cells, resulting in the incorporation of AQP2 into the membrane, finally increasing water reabsorption. This pathway can be altered by mutations in AVPR2 causing nephrogenic diabetes insipidus. In this study, we functionally characterize four mutations (R68W, ΔR67-G69/G107W, V162A and T273M) in AVPR2, which were found in Turkish patients. Upon AVP stimulation, R68W, ΔR67-G69/G107W and T273M showed a significantly reduced maximum in cAMP response compared to wild-type receptor. All mutant receptor proteins were expressed at the protein level; however, R68W, ΔR67-G69/G107W and T273M were partially retained in the cellular interior. Immunofluorescence studies showed that these mutant receptors were trapped in ER and Golgi apparatus. The function of V162A was indistinguishable from the indicating other defects causing disease. The results are important for understanding the influence of mutations on receptor function and cellular trafficking. Therefore, characterization of these mutations provides useful information for further studies addressing treatment of intracellularly trapped receptors with cell-permeable antagonists to restore receptor function in patients with nephrogenic diabetes insipidus.

Functional Characterization of Vasopressin Receptor 2 Mutations Causing Partial and Complete Congenital Nephrogenic Diabetes Insipidus in Thai Families

2010 ◽  
Vol 73 (5) ◽  
pp. 349-354 ◽  
Author(s):  
Taninee Sahakitrungruang ◽  
Meng Kian Tee ◽  
Natthakorn Rattanachartnarong ◽  
Vorasuk Shotelersuk ◽  
Kanya Suphapeetiporn ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Functional Characterization ◽  
Vasopressin Receptor ◽  
Congenital Nephrogenic Diabetes Insipidus
Sign in / Sign up

Export Citation Format

Share Document