Inhibition of dephosphorylation of the 20 kDa myosin light chain (MLC20) is an important
mechanism responsible for Ca2+-sensitization of vascular smooth muscle contraction. We
investigated whether this mechanism operates in prostaglandin F2α (PGF2α)-induced contraction
of rabbit aortic smooth muscle and, if so, which of protein kinase C (PKC) or Rho kinase
contributes to the inhibition of dephosphorylation. In normal medium, PGF2α (10 μM)
increased phosphorylation of MLC20 and developed tension. Rho kinase inhibitors fasudil and
hydroxyfasudil inhibited these changes, despite having no effect on a phorbol ester-induced
MLC20 phosphorylation. After treatment with verapamil or chelation of external Ca2+ with
EGTA, PGF2α increased the MLC20 phosphorylation and the tension without an increase in
[Ca2+]i, which were both sensitive to fasudil and hydroxyfasudil. ML-9, a MLC kinase inhibitor,
quickly reversed the KCl-induced MLC20 phosphorylation and contraction to the resting level.
However, fractions of PGF2α-induced contraction and MLC20 phosphorylation were resistant to
ML-9 but were sensitive to fasudil. Ro31-8220 (10 μM), a PKC inhibitor, did not affect the
MLC20 phosphorylation and the tension caused by PGF2α, excluding the possibility of
involvement of PKC in the PGF2α-induced MLC20 phosphorylation. PGF2α increased
phosphorylation at Thr654 of the myosin binding subunit (MBS) of myosin phosphatase, which
is a target of Rho kinase, and fasudil decreased the phosphorylation. These data suggest that the
PGF2α-induced contraction is accompanied by the inhibition of MLC20 dephosphorylation
through the MBS phosphorylation by Rho kinase, leading to Ca2+-sensitization of contraction.
Besides, an actin-associated mechanism may also be involved in the PGF2α-induced
sensitization.
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Essential role of Rho kinase in the Ca2+-sensitazation of prostaglandin F2α-induced contraction of rabbit aortae
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