Structure and function of V1b vasopressin receptor

Goto, Yukie (2010). Structure and function of V1b vasopressin receptor. University of Birmingham. Ph.D.

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Abstract

The V1b vasopressin receptor (V1bR) is a receptor for a neurohypophysial hormone [arginine8] vasopressin (AVP). V1bR is a G-protein coupled receptor (GPCR) belonging to the Family A GPCR superfamily. The structures of seven α-helical transmembrane domains of this family members can be predicted based on the crystal structure of bovine rhodopsin (bRho) and human β2 adrenergic receptor (β2AR) obtained by X-ray crystallography. This study aimed to identify amino acid residues which participate in ligand binding of the V1bR by site-directed mutagenesis with the aid of molecular models of vasopressin receptors based on the crystal structure of bRho.

The V1bR is a potential drug target in treating stress-related conditions such as depression, anxiety and post-traumatic stress disorders. Since it is the latest subtype identified among the mammalian neurohypophysial hormone receptors, it remains as the least studied subtype. A closely related subtype V1a receptor (V1aR) has been studied in far more detail for its potential of being a drug target in treating cardiac conditions and epilepsy. Hence, effective means of studying the V1bR can be accomplished by exploring the information already available on the V1aR and thereby defining the differences and similarities existing between the two. Detailed subtype comparisons are also fundamental for designing subtype selective drugs for effective therapy with fewer side-effects. This project was designed also to elucidate amino acid residues which determine selectivity of ligands for the V1bR over the V1aR.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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