20-HYDROXYEICOSATETRAENOIC ACID-INDUCED VASOCONSTRICTION AND INHIBITION OF POTASSIUM CURRENT IN CEREBRAL VASCULAR SMOOTH-MUSCLE IS DEPENDENT ON ACTIVATION OF PROTEIN-KINASE-C
A. Lange et al., 20-HYDROXYEICOSATETRAENOIC ACID-INDUCED VASOCONSTRICTION AND INHIBITION OF POTASSIUM CURRENT IN CEREBRAL VASCULAR SMOOTH-MUSCLE IS DEPENDENT ON ACTIVATION OF PROTEIN-KINASE-C, The Journal of biological chemistry, 272(43), 1997, pp. 27345-27352
20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 metabolit
e of arachidonic acid, is a potent vasoconstrictor, and has been impli
cated in the myogenic activation of renal and cerebral arteries. We ex
amined the role of protein kinase C (PKC) in the signal transduction p
athway by which 20-HETE induces vasoconstriction and inhibition of who
le-cell K+ current in cat cerebral vascular smooth muscle, 20-HETE ind
uced a concentration-dependent constriction in isolated pressurized ca
t middle cerebral arteries (-29 +/- 8% at 1 mu M). However, in the pre
sence of an N-myristoylated PKC pseudosubstrate inhibitor peptide (Myr
Psi PKC-I(19-27)) 20-HETE induced a concentration-dependent vasodilat
ion (26 +/- 4% at 1 mu M). In whole-cell voltage clamp studies, applic
ation of 20-HETE inhibited whole-cell K+ current recorded in cat cereb
ral vascular smooth muscle cells, an effect that was attenuated by Myr
Psi PKC-I(19-27). Further evidence for the role of PKC activation in
response to 20-HETE is the finding that 20-HETE increased the phosphor
ylation of myristoylated, alanine rich PKC substrate in cultured cat c
erebral vascular smooth muscle cells in a concentration-and PKC-depend
ent manner. These data provide evidence that PKC is an integral part o
f the signal transduction pathway by which 20-HETE elicits vasoconstri
ction of cerebral arteries and inhibition of whole-cell K+ current in
cat cerebral vascular smooth muscle.