Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression.
cGMP-based regulatory systems are vital for counteracting the renin-angiotensin system (RAS) which promotes volume expansion and high blood pressure. Natriuretic peptides and nitric oxide acting through their second messenger cGMP normally increase natriuresis and diuresis, and regulate renin release; however, the severe pathological state of cardiac heart failure is characterized by elevated levels of atrial natriuretic peptide that are no longer able to effectively oppose exaggerated RAS effects. There is presently limited information on the intracellular effectors of cGMP actions in the kidney. Recently we reported the cloning of the cDNA for type II cGMP-dependent protein kinase (cGK II), which is highly enriched in intestinal mucosa but was also detected for the first time in kidney. In the present study, cGK II was localized to juxtaglomerular (JG) cells, the ascending thin limb (ATL), and to a lesser extent the brush border of proximal tubules. An activator of renin gene expression, the angiotensin II type I receptor inhibitor, losartan, increased cGK II mRNA and protein three to fourfold in JG cells. In other experiments, water deprivation increased cGK II mRNA and protein three to fourfold in the inner medulla where both cGK II, and a kidney specific CI- channel shown by others to be regulated by dehydration, are localized in the ATL. Whereas additional data suggest that cGK I may primarily mediate cGMP-related changes in renal hemodynamics, cGK II may regulate renin release and ATL ion transport.
Gambaryan
S
S
Medizinische Universitäts-Klinik, Klinische Biochemie and Pathobiochemie, Würzburg, Germany.
Häusler
C
C
Markert
T
T
Pöhler
D
D
Jarchau
T
T
Walter
U
U
Haase
W
W
Kurtz
A
A
Lohmann
S M
SM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics*; D003681:Dehydration / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D019808:Losartan; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D002712:Chlorides; D007093:Imidazoles; D007527:Isoenzymes; D012333:RNA, Messenger; D013777:Tetrazoles; D009320:Atrial Natriuretic Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D012083:Renin; D019808:Losartan