title: Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption.
abstract: Aquaporin 2 (AQP2) is responsible for regulating the concentration of urine in the collecting tubules of the kidney under the control of vasopressin (Vp). Studies using Vp-deficient Brattleboro rats, however, indicated the existence of substantial Vp-independent mechanisms for membrane insertion, as well as transcriptional regulation, of this water channel. The Vp-independent mechanism(s) is clinically relevant to patients with X-linked nephrogenic diabetes insipidus (NDI) by therapeutically bypassing the dysfunctional Vp receptor. On the basis of studies with secretin receptor-null (SCTR(-/-)) mice, we report here for the first time that mutation of the SCTR gene could lead to mild polydipsia and polyuria. Additionally, SCTR(-/-) mice were shown to have reduced renal expression of AQP2 and AQP4, as well as altered glomerular and tubular morphology, suggesting possible disturbances in the filtration and/or water reabsorption process in these animals. By using SCTR(-/-) mice as controls and comparing them with wild-type animals, we performed both in vivo and in vitro studies that demonstrated a role for secretin in stimulating (i) AQP2 translocation from intracellular vesicles to the plasma membrane in renal medullary tubules and (ii) expression of this water channel under hyperosmotic conditions. The present study therefore provides information for at least one of the Vp-independent mechanisms that modulate the process of renal water reabsorption. Future investigations in this direction should be important in developing therapeutic means for treating NDI patients.
authors.affiliation: Department of Zoology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. bkcc@hkusua.hku.hk
authors.forename: Jessica Y S
authors.initials: JY
authors.lastname: Chu
authors.forename: Samuel C K
authors.initials: SC
authors.lastname: Chung
authors.forename: Amy K M
authors.initials: AK
authors.lastname: Lam
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Sookja K
authors.initials: SK
authors.lastname: Chung
authors.forename: Billy K C
authors.initials: BK
authors.lastname: Chow
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D051401:Aquaporin 4 / Q000378:metabolism; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011141:Polyuria / Q000235:genetics / Q000503:physiopathology; D021381:Protein Transport; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000502:physiology*; D012633:Secretin / Q000097:blood / Q000502:physiology*; D014867:Water / Q000378:metabolism*
chemical_list: C496024:Aqp2 protein, mouse; C496031:Aqp4 protein, mouse; D051399:Aquaporin 2; D051401:Aquaporin 4; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D014867:Water; D012633:Secretin