[Vasopressin receptors: structure/function relationships and signal transduction in target cells].
Vasopressin, a hypothalamic hormone, acts on its target tissues via three different G protein coupled receptors. The vasopressin V1a and V1b receptors, associated to Gq protein and phospholipase C, are responsible for vasoconstriction and regulation of the corticotroph axis respectively. The V2 vasopressin receptor is coupled to Gs protein and adenylyl cyclase and is responsible for water reabsorption in the renal collecting duct. Mutations of the V2 receptor are involved in diabetes insipidus and most of these mutations result in an endoplasmic reticulum (ER) retention of the mutated receptor. With the V1b receptor model, we have identified a proximal sequence of the C-terminal segment, which is crucial for ER export. Mutations in this short domain result in ER accumulation and degradation of the receptor. SSR 149415, a nonpeptide antagonist of V1bR, which is permeable to cell membrane, is able to rescue the mutant phenotype and acts as a pharmacological chaperone.
Robert
Jessica
J
Département d'Endocrinologie, Métabolisme et Cancer, Institut Cochin, INSERM U567, UMR 8104, CNRS, Université Paris V, Faculté de Médecine Cochin, 24, rue du Faubourg Saint-Jacques, 75014 Paris.
Clauser
Eacute Ric
ER
D000262:Adenylyl Cyclases / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002240:Carbohydrate Sequence; D002462:Cell Membrane / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics / Q000503:physiopathology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000502:physiology; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D021381:Protein Transport; D017483:Receptors, Vasopressin / Q000737:chemistry / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology; D014667:Vasopressins / Q000502:physiology*
D017483:Receptors, Vasopressin; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases