Downregulation of vasopressin V2 receptor promoter activity via V1a receptor pathway.
Vasopressin V(1a) and V(2) receptors (V(1a)R and V(2)R, respectively) distribute in the collecting duct of the kidney. Although the function of V(2)R mediating the antidiuretic effect of AVP has been investigated in detail, the role of V(1a)R in the collecting ducts has not been elucidated. In the present study, we have investigated the role of the V(1a)R pathway in V(2)R promoter activity. We cloned the 5'-flanking region of rat V(2)R (rV(2)R) and investigated rV(2)R promoter activity in the LLC-PK(1) cell line transfected to express rat V(1a)R (rV(1a)R) dominantly (LLC-PK(1)/rV(1a)R). AVP induced a transient increase, followed by a sustained decrease, of rV(2)R promoter activity in these cells. This AVP-induced decrease of rV(2)R promoter activity was inhibited by V(1a)R, but not V(2)R, antagonist. PMA mimicked this decrease of rV(2)R promoter activity. On the contrary, 8-(4-chlorophenylthio)-cAMP increased rV(2)R promoter activity. These PMA- and 8-(4-chlorophenylthio)-cAMP-induced effects were not observed on the deletion segment of the 5'-flanking region lacking CAAT and SP1 sites. In conclusion, 1) expression of the V(2)R is downregulated via the V(1a)R pathway in LLC-PK(1)/rV(1a)R cells, and 2) expression of the V(2)R is downregulated by the PMA-induced PKC pathway and upregulated by the cAMP-PKA pathway. These opposite effects of PKC and PKA appear to be regulated by the same promoter region of CAAT and SP1.
Izumi
Yuichiro
Y
Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, Kunamoto, Japan. 053r5110@med.stud.kumamoto-u.ac.jp
Nakayama
Yushi
Y
Mori
Tomohiko
T
Miyazaki
Hiroki
H
Inoue
Hideki
H
Kohda
Yukimasa
Y
Inoue
Takeaki
T
Nonoguchi
Hiroshi
H
Tomita
Kimio
K
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001483:Base Sequence; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D007425:Intracellular Membranes / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D018374:LLC-PK1 Cells; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017483:Receptors, Vasopressin / Q000235:genetics* / Q000502:physiology*; D020218:Response Elements; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014162:Transfection
D017483:Receptors, Vasopressin; D013873:Thionucleotides; D001127:Arginine Vasopressin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate