{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:21:22Z","timestamp":1790936482365,"version":"4.1.0"},"reference-count":24,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In most cases, nephrogenic diabetes insipidus results from mutations in the V2 vasopressin receptor (V2R) gene that cause intracellular retention of improperly folded receptors. We previously reported that cell permeable V2R antagonists act as pharmacological chaperones that rescue folding, trafficking, and function of several V2R mutants. More recently, the vasopressin antagonist, SR49059, was found to be therapeutically active in nephrogenic diabetes insipidus patients. Three of the patients with positive responses harbored the mutation R137H, previously reported to lead to constitutive endocytosis. This raises the possibility that, instead of acting as a pharmacological chaperone by favoring proper maturation of the receptors, SR49059 could mediate its action on R137H V2R by preventing its endocytosis. Here we report that the \u03b2-arrestin-mediated constitutive endocytosis of R137H V2R is not affected by SR49059, indicating that the functional rescue observed does not result from a stabilization of the receptor at the cell surface. Moreover, metabolic labeling revealed that R137H V2R is also poorly processed to the mature form. SR49059 treatment significantly improved its maturation and cell surface targeting, indicating that the functional rescue of R137H V2Rs results from the pharmacological chaperone action of the antagonist.<\/jats:p>","DOI":"10.1210\/me.2004-0080","type":"journal-article","created":{"date-parts":[[2004,6,1]],"date-time":"2004-06-01T00:33:46Z","timestamp":1086050026000},"page":"2074-2084","source":"Crossref","is-referenced-by-count":132,"title":["Functional Rescue of the Constitutively Internalized V2 Vasopressin Receptor Mutant R137H by the Pharmacological Chaperone Action of SR49059"],"prefix":"10.1210","volume":"18","author":[{"given":"Virginie","family":"Bernier","sequence":"first","affiliation":[{"name":"De\u0301partement de Biochimie and Groupe de Recherche sur le Syste\u0300me Nerveux Autonome (V.B., M.La., M.B.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada H3C 3J7"},{"name":"Unite\u0301 de Recherche Clinique and De\u0301partement de Me\u0301decine (V.B., M.Lo., M.-F.A., D.G.B.), Centre de Recherche et Service de Ne\u0301phrologie, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada H4J 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Lagace\u0301","sequence":"additional","affiliation":[{"name":"De\u0301partement de Biochimie and Groupe de Recherche sur le Syste\u0300me Nerveux Autonome (V.B., M.La., M.B.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada H3C 3J7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miche\u0300le","family":"Lonergan","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherche Clinique and De\u0301partement de Me\u0301decine (V.B., M.Lo., M.-F.A., D.G.B.), Centre de Recherche et Service de Ne\u0301phrologie, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada H4J 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Franc\u0327oise","family":"Arthus","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherche Clinique and De\u0301partement de Me\u0301decine (V.B., M.Lo., M.-F.A., D.G.B.), Centre de Recherche et Service de Ne\u0301phrologie, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada H4J 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Bichet","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Recherche Clinique and De\u0301partement de Me\u0301decine (V.B., M.Lo., M.-F.A., D.G.B.), Centre de Recherche et Service de Ne\u0301phrologie, Ho\u0302pital du Sacre\u0301-C\u0153ur de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada H4J 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Bouvier","sequence":"additional","affiliation":[{"name":"De\u0301partement de Biochimie and Groupe de Recherche sur le Syste\u0300me Nerveux Autonome (V.B., M.La., M.B.), Universite\u0301 de Montre\u0301al, Montre\u0301al, Que\u0301bec, Canada H3C 3J7"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614210912200_R1","doi-asserted-by":"crossref","first-page":"E207","DOI":"10.1038\/35041139","article-title":"Conformational disease.","volume":"2","author":"Kopito","year":"2000","journal-title":"Nat Cell Biol"},{"key":"2020071614210912200_R2","first-page":"4181","article-title":"Nephrogenic diabetes insipidus.","author":"Bichet","year":"2001"},{"key":"2020071614210912200_R3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1146\/annurev.physiol.63.1.607","article-title":"Nephrogenic diabetes insipidus.","volume":"63","author":"Morello","year":"2001","journal-title":"Annu Rev Physiol"},{"key":"2020071614210912200_R4","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1172\/JCI8688","article-title":"Pharmacological 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