Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption

Autor: Sookja K. Chung, Sidney Tam, Samuel C. K. Chung, Amy K. M. Lam, Billy K. C. Chow, Jessica Y. S. Chu
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Vasopressin
Kidney Glomerulus
Receptors
G-Protein-Coupled - genetics - physiology
urologic and male genital diseases
Secretin
Receptors
G-Protein-Coupled
Kidney Tubules - metabolism - pathology
Mice
Kidney Glomerulus - metabolism - pathology
Receptors
Gastrointestinal Hormone - genetics - physiology
Mice
Knockout
Kidney
Reabsorption
Articles
Aquaporin 4 - metabolism
Protein Transport
Aquaporin 4
medicine.anatomical_structure
Kidney Tubules
Phenotype
Aquaporin 2
Secretin receptor
medicine.medical_specialty
Cell Membrane - metabolism
Molecular Sequence Data
Biological Transport
Active
Biology
Secretin - blood - physiology
Receptors
Gastrointestinal Hormone
Water - metabolism
Cytoplasmic Vesicles - metabolism
Aquaporin 2 - metabolism
Internal medicine
medicine
Animals
Amino Acid Sequence
Molecular Biology
Polyuria
Cell Membrane
Cytoplasmic Vesicles
Water
Cell Biology
Polyuria - genetics - physiopathology
Nephrogenic diabetes insipidus
medicine.disease
Rats
Endocrinology
Mutation
Popis: 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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