Xie H, Laher I, Bevan J A
Department of Pharmacology, College of Medicine, University of Vermont, burlington, USA.
J Pharmacol Exp Ther. 1996 Nov;279(2):668-74.
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.
