Development of a human vasopressin V_1a-receptor antagonist from an evolutionary-related insect neuropeptide.

ABSTRACT: Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V_1b receptors, but inhibited the human V

SUBMITTER: Di Giglio MG 

PROVIDER: S-EPMC5286520 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature