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Adenylate Cyclase 6 Determines cAMP Formation and Aquaporin-2 Phosphorylation and Trafficking in Inner Medulla
- Source :
- Rieg, T, Tang, T, Murray, F, Schroth, J, Insel, P A, Fenton, R A, Hammond, H K & Vallon, V 2010, ' Adenylate cyclase 6 determines cAMP formation and aquaporin-2 phosphorylation and trafficking in inner medulla ', Journal of the American Society of Nephrology, vol. 21, no. 12, pp. 2059-68 . https://doi.org/10.1681/ASN.2010040409
- Publication Year :
- 2010
- Publisher :
- American Society of Nephrology, 2010.
-
Abstract
- Arginine vasopressin (AVP) enhances water reabsorption in the renal collecting duct by vasopressin V₂ receptor (V₂R)-mediated activation of adenylyl cyclase (AC), cAMP-promoted phosphorylation of aquaporin-2 (AQP2), and increased abundance of AQP2 on the apical membrane. Multiple isoforms of adenylate cyclase exist, and the roles of individual AC isoforms in water homeostasis are not well understood. Here, we found that levels of AC6 mRNA, the most highly expressed AC isoform in the inner medulla, inversely correlate with fluid intake. Moreover, mice lacking AC6 had lower levels of inner medullary cAMP, reduced abundance of phosphorylated AQP2 (at both serine-256 and serine-269), and lower urine osmolality than wild-type mice. Water deprivation or administration of the V₂R agonist dDAVP did not increase urine osmolality of AC6-deficient mice to the levels of wild-type mice. Furthermore, AC6-deficient mice lacked dDAVP-promoted inner medullary cAMP formation and phosphorylation of serine-269 and had attenuated increases in both phosphorylation of serine-256 and apical membrane AQP2 trafficking. In summary, AC6 expression determines inner medullary cAMP formation and AQP2 phosphorylation and trafficking, the absence of which causes nephrogenic diabetes insipidus.
- Subjects :
- Adenylate Cyclase
Vasopressin
medicine.medical_specialty
Blotting, Western
Adenylate kinase
Diabetes Insipidus, Nephrogenic
Mice, Inbred Strains
Biology
urologic and male genital diseases
Cyclase
Polymerase Chain Reaction
Sensitivity and Specificity
Adenylyl cyclase
chemistry.chemical_compound
Mice
Random Allocation
Internal medicine
Arginine vasopressin receptor 2
medicine
Cyclic AMP
Animals
Deamino Arginine Vasopressin
RNA, Messenger
Kidney Tubules, Collecting
Phosphorylation
Kidney Medulla
Aquaporin 2
Water Deprivation
urogenital system
Osmolar Concentration
General Medicine
Apical membrane
Water-Electrolyte Balance
Arginine Vasopressin
Disease Models, Animal
Endocrinology
Basic Research
chemistry
Nephrology
Adenylyl Cyclases
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Rieg, T, Tang, T, Murray, F, Schroth, J, Insel, P A, Fenton, R A, Hammond, H K & Vallon, V 2010, ' Adenylate cyclase 6 determines cAMP formation and aquaporin-2 phosphorylation and trafficking in inner medulla ', Journal of the American Society of Nephrology, vol. 21, no. 12, pp. 2059-68 . https://doi.org/10.1681/ASN.2010040409
- Accession number :
- edsair.doi.dedup.....7a309556f287bd4224054273ce89b595