Protein kinase C modulates flow-initiated contraction.
The objective of this study was to determine whether protein kinase C (PKC) activation is involved, and what its role might be, in flow-induced contraction. Contractions induced by flow (40 microliters/min), K+ (25 mM) and histamine (300 nM) in segments of the rabbit fatal vein were compared under isometric conditions. The PKC activator 12-O-tetradecanoylphorbol-13-acetate (50 nM) significantly enhanced flow-induced and K(+)-induced, but not histamine-induced, contractions. Down-regulation of PKC by preincubation with phorbol 1,13-dibutyrate (10 nM for 24 hr) markedly inhibited flow contraction. Although histamine-induced contraction was also affected, the response to K+ remained unchanged. The potentiation of flow-induced contraction by 12-O-tetradecanoylphorbol-13-acetate was prevented by the voltage-gated Ca+2 channel antagonist diltiazem (1 microM). When the PKC activator 12-O-tetradecanoylphorbol-13-acetate (50 nM) was added in a Ca(+2)-free medium containing manganese (1 mM), flow-induced and 25 mM K(+)-induced contractions were enhanced and unaltered, respectively, but histamine-induced contraction was reduced. It is argued that of three types of contractions studied, PKC predominantly modulates flow-induced contraction. PKC can influence this contraction through increases in both Ca++ entry and Ca++ sensitivity.
Xie
H
H
Department of Pharmacology, College of Medicine, University of Vermont, burlington, USA.
Laher
I
I
Bevan
J A
JA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D012039:Regional Blood Flow; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction
D015240:Phorbol 12,13-Dibutyrate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium