Pathophysiological role of aquaporin-2 in impaired water excretion.
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.
Ishikawa
San-E
SE
Department of Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan.
Saito
Tomoyuki
T
Saito
Takako
T
Kasono
Keizo
K
Funayama
Hiroshi
H
D000818:Animals; D051399:Aquaporin 2 / Q000235:genetics* / Q000502:physiology*; D001127:Arginine Vasopressin / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006333:Heart Failure / Q000503:physiopathology; D007177:Inappropriate ADH Syndrome / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D008156:Luciferases / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014883:Water-Electrolyte Imbalance / Q000503:physiopathology*
D051399:Aquaporin 2; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D003994:Bucladesine; D008156:Luciferases; D003894:Deamino Arginine Vasopressin