Endocrine Abstracts

Diabetes insipidus (DI) is a disorder that characterized by producing large volume of urine for daily due to the problems at the arginine vasopressin (AVP-NPII), aquaporin 2 (AQP2) and arginine vasopressin receptor 2 (AVPR2) genes. These problems can be inherited or acquired. Among these genes, AVPR2 is a G protein coupled receptor and most of the inherited type of DI are caused by mutations in AVPR2 gene. Mutations can cause improper folding of the receptor protein and this situation causes to retention of the protein in cellular compartments such as endoplasmic reticulum (ER) or Golgi apparatus. For treatment strategies, researchers try to use chemicals to rescue of mutant proteins from the control mechanisms to make them at least functional. In this study, we aimed to do pre-research for the rescuing mutant receptors (R68W, V162A, T273M, R67_G69del/G107W, V88M, R106C, G12E). We performed functional characterization of these mutant receptors in our previous study and they were observed as trapped in the ER or Golgi apparatus. In the present study, COS-7 cells were transfected with mutant and wild type AVPR2s. 48 hours after the transfection, different concentrations of DMSO and glycerol were performed to the cells. 16–18 hours after the treatment of DMSO and glycerol, cell surface ELISA were performed to understand cell surface expression of the mutant proteins when they were treated with different concentrations of DMSO and glycerol. According to the ELISA results, mutant receptors showed different rescue profile compared to the wild type receptor. As a result, we can say that rescuing trapped mutant receptors from ER or Golgi apparatus control mechanisms using with chemicals could be a forward step for the treatment of DI. Receptors that have mutations which cause retention in ER or Golgi apparatus may be functional if they are rescued by chemicals. For further studies, instead of chemicals, pharmacochaperons could be use. We can conclude that, rescue studies of mutated proteins by using chemicals or pharmacochaperons shed light to the treatment strategies of DI. This work was supported by The Scientific and Technological Research Council of Turkey (Project Numbers: 216S304 and 112S513).