Inhibition of protein kinases A and G by hydralazine but not KRN2391 in vitro.
OBJECTIVE
To examine possible direct effects of the vasodilators hydralazine and KRN2391 on the activities of protein kinase A (PKA), protein kinase G (PKG), and protein kinase C (PKC).


METHODS
PKA, PKG and PKC were extracted from bovine lung, heart and rat brain and purified to homogeneity by chromatography. The effects of different reagents on these protein kinase activities were determined in vitro.


RESULTS
Hydralazine (0.03-10 mmol.L(-1)) inhibited the activities of both PKA and PKG with IC50 of 1.2 and 2.5 mmol.L(-1), respectively, but had little effect on PKC. KRN2391 (1-1000 mumol.L(-1) had no effects on PKA, PKG, or PKC. Using H-89 and GF109203X, inhibitors relatively selective to PKA and PKC respectively, as controls, we obtained inhibitions on PKG, PKA, and PKC similar to literature. However, a novel PKG inhibitor KT5823 failed to inhibit PKG or PKA.


CONCLUSIONS
Hydralazine alters the activity of PKG and PKA, which may have implications for the vasodilator activity.
Sun
G
G
Endocrine Unit, John Hunter Hospital, Newcastle, NSW, Australia.
Robinson
P J
PJ
D000818:Animals; D002417:Cattle; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006830:Hydralazine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011725:Pyridines; D014665:Vasodilator Agents; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D006830:Hydralazine; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C