Abstract
Nephrogenic Diabetes Insipidus is a rare disorder which is characterized by severe water imbalance in the body. The disease can be acquired or inherited. AVPR2 (arginine vasopressin type 2 receptor) mutations are responsible for genetical type of the disorder. Mutations in the AVPR2 gene may cause loss-of-function due to conformational defects. According to the mutation type, the three-dimensional structure of AVPR2 may be affected even if it is functional and therefore it may not reach the plasma membrane where it is functional. Consequently, it is generally trapped in the Endoplasmic reticulum or Golgi apparatus, which are the quality control systems of the cell. Pharmacological chaperones have been used to retrieve these mutant AVPR2s from these quality control systems of the cell and take them to the plasma membrane for therapeutic purposes. In this study, in order to analyze the effects of two pharmacological chaperones, SR121463B and SR49059, we performed total ELISA and surface ELISA studies and cAMP accumulation assays on mutant receptors (G12E, R68W, V88M, ΔR67_G69/G107W, R106C, V162A and T273M). We observed that pharmacological chaperones may act differently on mutated AVPR2s. Cell surface expression of the mutant receptors and cAMP accumulation response, after stimulation with AVP, were mostly improved by these pharmacological chaperones. We believe that, this study presents important results with respect to the process of the variable type of mutated proteins in the cell and may help in developing a process of new types of chaperones.
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