scholarly journals Synthesis and Characterization of Orally Active Nonpeptide Vasopressin V2 Receptor Antagonists.

1999 ◽  
Vol 47 (4) ◽  
pp. 501-510 ◽  
Author(s):  
Takehiko OHKAWA ◽  
Tatsuya ZENKOH ◽  
Masayuki TOMITA ◽  
Naomi HOSOGAI ◽  
Keiji HEMMI ◽  
...  
Keyword(s):  
Synthesis And Characterization ◽  
Receptor Antagonists ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor ◽  
Orally Active

ChemInform Abstract: Synthesis and Characterization of Orally Active Nonpeptide Vasopressin V2 Receptor Antagonists.

ChemInform ◽  
2010 ◽  
Vol 30 (42) ◽  
pp. no-no
Author(s):  
Takehiko Ohkawa ◽  
Tatsuya Zenkoh ◽  
Masayuki Tomita ◽  
Naomi Hosogai ◽  
Keiji Hemmi ◽  
...  
Keyword(s):  
Synthesis And Characterization ◽  
Receptor Antagonists ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor ◽  
Orally Active

Synthesis and Characterization of Pseudopeptide Bradykinin B2 Receptor Antagonists Containing the 1,3,8-Triazaspiro[4.5]decan-4-one Ring System

1996 ◽  
Vol 39 (16) ◽  
pp. 3169-3173 ◽  
Author(s):  
Babu J. Mavunkel ◽  
Zhijian Lu ◽  
R. Richard Goehring ◽  
Songfeng Lu ◽  
Sarvajit Chakravarty ◽  
...  
Keyword(s):  
Ring System ◽  
Synthesis And Characterization ◽  
Receptor Antagonists ◽  
Bradykinin B2 Receptor

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.

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