Pathophysiological role of aquaporin-2 in impaired water excretion.

Abstract

In a state of chronic arginine vasopressin (AVP)-induced antidiuresis, the antidiuretic efficacy has been attenuated: a phenomenon known as "AVP escape". We compared the experimental SIADH rats with 1-deamino-8-D-AVP (dDAVP)-excess rats. The SIADH rats, but not the dDAVP-excess rats, showed a marked attenuation of urinary concentrating ability. This is closely associated with diminished up-regulation of aquaporin-2 (AQP-2) mRNA and protein expression. The following in vitro study clarified tonicity-response elements in the 5'-flanking region of AQP-2 gene. There are at least more than two hypertonicity-response elements, and a hypotonicity-response element resided at tonicity-response enhancer (TonE) (-570 to -560bp) in the AQP-2 gene. Hypotonicity directly reduced the cAMP-induced AQP-2 promoter activity by mediating JNK kinase. Reduction in transcriptional regulation of AQP-2 under hypotonic state may support the in vivo finding of AVP escape phenomenon in chronic AVP-induced antidiuresis.

• Authors: San-E Ishikawa, Tomoyuki Saito, Takako Saito, Keizo Kasono, Hiroshi Funayama
• Journal: Progress in brain research (Prog Brain Res) Vol. 170 Pg. 581-8 ( 2008) ISSN: 1875-7855 [Electronic] Netherlands
• PMID: 18655911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aquaporin 2
• RNA, Messenger
• Arginine Vasopressin
• Bucladesine
• Luciferases
• Deamino Arginine Vasopressin

Topics

• Animals
• Aquaporin 2 (genetics, physiology)
• Arginine Vasopressin (pharmacology)
• Bucladesine (pharmacology)
• Deamino Arginine Vasopressin (pharmacology)
• Disease Models, Animal
• Diuresis (drug effects, physiology)
• Gene Expression Regulation
• Genes, Reporter
• Heart Failure (physiopathology)
• Inappropriate ADH Syndrome (physiopathology)
• Kidney (physiopathology)
• Luciferases (genetics)
• Promoter Regions, Genetic
• RNA, Messenger (genetics)
• Rats
• Water-Electrolyte Imbalance (physiopathology)