In:
The Journal of Physiology, Wiley, Vol. 546, No. 3 ( 2003-02), p. 823-836
Abstract:
Inhibition of dephosphorylation of the 20 kDa myosin light chain (MLC 20 ) is an important mechanism for the Ca 2+ ‐induced sensitization of vascular smooth muscle contraction. We investigated whether this mechanism operates in prostaglandin F 2α (PGF 2α )‐induced contraction of rabbit aortic smooth muscle and, if so, whether protein kinase C (PKC) or rho‐associated kinase (rho kinase) contribute to the inhibition of dephosphorylation. In normal medium, PGF 2α (10 μ m ) increased the phosphorylation of MLC 20 and developed tension. The rho‐kinase inhibitors fasudil and hydroxyfasudil inhibited these changes, despite having no effect on a phorbol‐ester‐induced MLC 20 phosphorylation. After treatment with verapamil or chelation of external Ca 2+ with EGTA, PGF 2α increased the MLC 20 phosphorylation and tension without an increase in [Ca 2+ ] i , all of which were sensitive to fasudil and hydroxyfasudil. ML‐9, a MLC kinase inhibitor, quickly reversed the KCl‐induced MLC 20 phosphorylation and contraction to the resting level. However, fractions of PGF 2α ‐induced contraction and MLC 20 phosphorylation were resistant to ML‐9 but were sensitive to fasudil. Ro31‐8220 (10 μ m ), a PKC inhibitor, did not affect the phosphorylation of MLC 20 and the tension caused by PGF 2α , thus excluding the possibility of the involvement of PKC in the PGF 2α ‐induced MLC 20 phosphorylation. PGF 2α 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 PGF 2α ‐induced contraction is accompanied by the inhibition of MLC 20 dephosphorylation through rho kinase‐induced MBS phosphorylation, leading to Ca 2+ sensitization of contraction. An actin‐associated mechanism may also be involved in the PGF 2α ‐induced sensitization.
Type of Medium:
Online Resource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/jphysiol.2002.030775
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
1475290-6
SSG:
12
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