TPA-induced contraction of isolated rabbit vascular smooth muscle.
Myosin light chain phosphorylation may not regulate the sustained phase of vascular smooth muscle contraction. Another, unidentified, calcium-dependent pathway may be involved in this process. TPA, an activator of C-kinase, at concentrations of 10 to 333 nM induces a calcium-dependent contraction of vascular smooth muscle which develops slowly but progressively to reach values of 50-300 mm Hg. Arteries exposed to the ionophore A23187, in a calcium-free medium, display a uniform series of contractile responses when exposed to 1.5 mM Ca2+ for 2 min once every 10 min. Exposure to 100 nM TPA as well as ionophore leads to a progressive enhancement of these calcium-induced, contractile responses. Arteries stimulated by brief (10 sec), repetitive (every 3 min) electrical pulses, respond with a series of comparable phase 1 responses. Prior exposure of vessels to 10 nM TPA, causes a progressive increase in the magnitude of these responses to repetitive electrical stimulation. Addition of 25 microM forskolin, an activator of adenylate cyclase, to TPA-treated, partially-contracted muscle leads to the immediate inhibition of the TPA-induced contraction. These data suggest that the activation of C-kinase plays a significant role in regulating vascular smooth muscle contraction.
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004224:Diterpenes; D010704:Phorbols; D005576:Colforsin; D000001:Calcimycin; D011494:Protein Kinases; D009219:Myosin-Light-Chain Kinase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium