Essential role of rho kinase in the XXXX sensitization of @entity3774 -induced contraction of @entity95 aortae.

@entity8232 @entity1855 @entity4527 @entity95 @entity7131 @entity2701 @entity4621 @entity36243 @entity20383 @entity3774 @entity13293 @entity141 @entity25387 @entity4338
Inhibition of dephosphorylation of the 20 kDa myosin light chain (MLC(20)) is an important mechanism for the @entity141 -induced sensitization of vascular smooth muscle contraction. We investigated whether this mechanism operates in @entity3774 (PGF(2alpha))-induced contraction of @entity95 aortic smooth muscle and, if so, whether @entity7131 ( @entity7131 ) or rho-associated kinase (rho kinase) contribute to the inhibition of dephosphorylation. In normal medium, @entity3774 (10 microM) increased the phosphorylation of MLC(20) and developed @entity2701 . The rho-kinase inhibitors @entity8232 and @entity36243 inhibited these changes, despite having no effect on a @entity4621 -induced MLC(20) phosphorylation. After treatment with @entity1855 or chelation of external @entity141 with @entity4527 , @entity3774 increased the MLC(20) phosphorylation and @entity2701 without an increase in [ @entity141 ](i), all of which were sensitive to @entity8232 and @entity36243 . @entity13293 , a MLC kinase inhibitor, quickly reversed the @entity4338 -induced MLC(20) phosphorylation and contraction to the resting level. However, fractions of PGF(2alpha)-induced contraction and MLC(20) phosphorylation were resistant to @entity13293 but were sensitive to @entity8232 . @entity25387 (10 microM), a @entity7131 inhibitor, did not affect the phosphorylation of MLC(20) and the @entity2701 caused by PGF(2alpha), thus excluding the possibility of the involvement of @entity7131 in the PGF(2alpha)-induced MLC(20) phosphorylation. PGF(2alpha) increased phosphorylation at Thr654 of the @entity20383 ( @entity20383 ) of myosin phosphatase, which is a target of rho kinase, and @entity8232 decreased the phosphorylation. These data suggest that the PGF(2alpha)-induced contraction is accompanied by the inhibition of MLC(20) dephosphorylation through rho kinase-induced @entity20383 phosphorylation, leading to @entity141 sensitization of contraction. An actin-associated mechanism may also be involved in the PGF(2alpha)-induced sensitization.
