Effects of staurosporine and calphostin C, two structurally unrelated inhibitors of protein kinase C, on vascular tone.
In isolated rings of the rabbit facial vein, facial artery, and aorta, calphostin C and staurosporine, inhibitors of protein kinase C, reduced myogenic tone and norepinephrine (1 microM), K+ (80 mM), and Ca2+ (1.6 mM) induced tone. In all instances, staurosporine was more potent than calphostin C. In contrast to staurosporine, the IC50 value of calphostin C against myogenic tone was similar to that recorded for protein kinase C in biochemical studies (0.086 vs. 0.050 microM) and the average IC50 values of calphostin C against norepinephrine (2.2 microM), K+ (3.3 microM), and Ca2+ (4.3 microM) in the three vessels were similar to that for myosin light-chain kinase in biochemical studies (> 5.0 microM). In the facial vein, calphostin C was 59-fold more potent against myogenic tone than against Ca(2+)-induced tone and 8-fold more specific for myogenic tone than was staurosporine. In addition, at concentrations not affecting K+ (80 mM) induced tone, calphostin C suppressed 1-oleoyl-2-acetyl-sn-glycerol induced tone in the facial vein, whereas staurosporine only attenuated it by 65%. Thus calphostin C inhibits protein kinase C dependent tone in isolated blood vessels to a greater extent than does staurosporine.
Henrion
D
D
Department of Pharmacology, University of Vermont, College of Medicine, Burlington 05405-0068.
Laher
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I
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D005145:Face / Q000098:blood supply; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009281:Naphthalenes; D009638:Norepinephrine / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012680:Sensitivity and Specificity; D019311:Staurosporine
D000470:Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D009638:Norepinephrine