Elevated renal cortical calmodulin-dependent protein kinase activity and blood pressure.
The spontaneously hypertensive rat (SHR) exhibits not only hypertension but also behavioral hyperactivity which are not genetically linked. Two strains of rats, one hypertensive but normoactive (WKHT) and another, hyperactive but normotensive (WKHA), have been generated from SHR. We have reported that in renal proximal tubules, the linkage between D1-like receptors an adenylyl cyclase was impaired in SHR and WKHT but intact in WKHA. The impaired renal D1-like receptor function in the SHR was associated with increased phosphorylation of the D1 receptor, presumably caused by increased phosphorylation by G protein-coupled receptor kinases (GRK) or decreased dephosphorylation by protein phosphatase 2A. Because calmodulin kinase (CaMK) can regulate GRK activity, CaMK activity in renal cortical membranes of WKHA and WKHT were studied. We found that CaMK-dependent phosphorylation was two-fold higher in WKHA than in WKHT. In addition, serine phosphorylation of a 36 KDa and a 24 KDa protein was 5-fold and 3-fold greater in WKHA than in WKHT. We hypothesize that the increased CaMK activity in the renal cortical membrane may serve to inhibit GRK activity in WKHA and prevent the development of hypertension.
Lao
Yuen-Sum
YS
School of Pharmacy, University of Missouri-Kansas City, USA.
Hendley
Edith D
ED
Felder
Robin A
RA
Jose
Pedro A
PA
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
D017447:Receptors, Dopamine D1; D017871:Calcium-Calmodulin-Dependent Protein Kinases