Endocrine Abstracts

Nefrojenic Diabetes insipidus is one of the typical conformational disorders result from protein misfolding and degredation or aggregation due to the mutations in AVPR2. The patients of nephrogenic Diabetes insipidus have difficulty in concentrate of urine and because of this, they have polyuria, hypoosmolar urine and hypernatremia in variable levels. To make them relieved, many treatment strategies have been studying and using dDAVP nasally is one of these strategies. Another treatment approach on this type of conformational disease is in vitro treatment of mutant AVPR2s with pharmacological chaperones (PCs). PCs are small molecules that bind to misfolded proteins and stabilize them and rescue these mutated proteins from quality control system of Endoplasmic reticulum. In this study, Tolvaptan; OPC-41 061, Mozavaptan; OPC-31 260 and OPC-21 268 were selected as pharmacological chaperones for treatment of previously identified and functionally analyzed mutations (R68W, DR67_G69/G107W and T273M) by our group. As a functional analysis, we performed cell surface ELISA after the treatment of mutant AVPR2s with OPC-41 061, OPC-31 260 and OPC-21 268. Our study was supported by The Scientific and Technological Research Council of Turkey (SBAG Project number 216S304). According to the ELISA results, some mutant AVPR2s could be rescued after the treatment with OPC-41 061, OPC-31 260 and OPC-21 268, separately. In conclusion, we think that using pharmacological chaperones in vitro has an importance on developing treatment strategies for these kind of conformational disorders. In the future, we will perform more functional analysis experiments on these mutants after the treatment with OPC-41 061, OPC-31 260 and OPC-21 268, separately. Consequently, all these analysis will make us to understand the precise affect of OPC-41 061, OPC-31 260 and OPC-21 268 in vitro.