V2-1 항이뇨홀몬 합성수용체의 구조적 특성에 관한 연구 = Studies on the structural characteristics of V2-1 chimeric vasopressin receptor

다국어 초록 (Multilingual Abstract)

In this study, in order to evaluate the structural characteristics of the vasopressin receptor, it was tried to construct the V2-V1 chimeric vasopressin recepter and to compare its pharmacological natures to the natural receptors.
The 2nd and 3rd extracellular loop of V2 receptor was substituted to that of V1b receptor using polymerase chain reaction (PCR) and the changes in binding affinity of vasopressin as well as the changes in intracytosolic effector pathways were observed.
The V2-V1 chimeric receptor showed a greatly decreased hormone binding affinity compared to that of natural receptors (3% of the V2 receptor and 10% of the V1b receptor) and also completely lost the intracellular effect to produce cAMP in transfected COS-7 cells. On the while, the chimeric receptor still reserved the ability to produce IP3 inside the COS-7 cells (35% of V1b receptor), which indicates that the effector pathwas for IP3 production is still available in chimeric receptor.
These results suggest that binding of vasopressin to its receptor is determined not by the specific partial amino acid sequence, but by the entire extracellualr protein structure of the receptor. Also suggested is that binding of vasopressin receptor to G protein is governed mainly by th 2nd or 3rd intracytosolic loop structure. These studies could contribute to the development of antagonistic pharmaceuticals, which will act as antihypertensive or antidiuretics, through the evaluation of structural characteristics of vasopressin receptor.