Downregulation of the V2 vasopressin receptor in dehydration: mechanisms and role of renal prostaglandin synthesis.
The vasopressin-aquaporin 2 system plays a key role in urine concentration in dehydration. In contrast to the upregulation of aquaporin 2, the downregulation of the vasopressin V2 receptor in dehydration is known. We investigated the mechanisms of this downregulation in dehydration using reverse transcription-competitive polymerase chain reaction (RT-competitive PCR) and Western blot analysis. The incubation of microdissected inner medullary collecting ducts (IMCDs) in a hypertonic medium or with vasopressin stimulated V2 receptor mRNA and protein expression, showing that dehydration-induced hyperosmolality in renal medulla and increased plasma arginine vasopressin (AVP) concentration should upregulate V2 receptor. The presence of inhibitory factors on the V2 receptor in dehydration was suggested. Prostaglandin E(2) (PGE(2)) is known to inhibit AVP-induced cAMP production and to increase production in dehydration. PGE(2) slightly stimulated V2 receptor mRNA expression in IMCD in vitro. However, PGE(2) inhibited V2 receptor mRNA expression in IMCD in the presence of 10(-9) M vasopressin. The blockade of PGE(2) synthesis by indomethacin in dehydrated rats increased V2 receptor protein expression after 24-48 h with an early increase in V2 receptor mRNA expression. In summary, these data suggest that increased production of PGE(2) in renal medulla plays a key role in the downregulation of V2 receptor in dehydration.
Machida
Kenji
K
Dept. of Nephrology, Kumamoto Univ. Graduate School of Medical Sciences, Kumamoto, Kumamoto 860-8556, Japan.
Wakamatsu
Shiho
S
Izumi
Yuichiro
Y
Yosifovska
Tatjana
T
Matsuzaki
Takanobu
T
Nakayama
Yushi
Y
Kohda
Yukimasa
Y
Inoue
Takeaki
T
Saito
Hideyuki
H
Tomita
Kimio
K
Nonoguchi
Hiroshi
H
D000818:Animals; D051399:Aquaporin 2 / Q000096:biosynthesis; D001127:Arginine Vasopressin / Q000494:pharmacology; D003681:Dehydration / Q000503:physiopathology*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000502:physiology / Q000652:urine; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000096:biosynthesis*; D014556:Urine / Q000502:physiology
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D015232:Dinoprostone; D007213:Indomethacin