Smooth-muscle contraction is regulated by the cytosolic Ca2þ
concentration and by the calcium sensitivity of myofilaments. The
cytosolic Ca2þ activates myosin light-chain kinase and the sensitivity
of myofilaments is achieved by the inhibition of myosin
light chain phosphatase (MLC phosphatase) through RhoA/Rhokinase
pathway. RhoA a small GTPase stimulates Rho-kinase 2
(ROCK-II), which then inhibits myosin light chain phosphatase
(MLC phosphatase) by phosphorylating it. MLC phosphatase
converts active myosin light chain (MLC-P) to inactive myosin
light chain (MLC) resulting in relaxtion of the tissue. MLC
phosphatase when inhibited increases the gain or sensitivity of
myosin light chain kinase to calcium. Thus inhibition of MLC
phosphatase by ROCK-II enzyme promotes contraction of
smooth muscle through calcium sensitization (Uehata et al.,
1997; Gohla et al., 2000; Somlyo and Somlyo, 2000). In addition,
RhoA/Rho-kinase suppresses endothelial nitric oxide synthase
(eNOS) inhibiting NO/cGMP pathway involved in relaxation of
corpus cavernosum smooth muscle (Bivalacqua et al., 2004)
Smooth-muscle contraction is regulated by the cytosolic Ca2þconcentration and by the calcium sensitivity of myofilaments. Thecytosolic Ca2þ activates myosin light-chain kinase and the sensitivityof myofilaments is achieved by the inhibition of myosinlight chain phosphatase (MLC phosphatase) through RhoA/Rhokinasepathway. RhoA a small GTPase stimulates Rho-kinase 2(ROCK-II), which then inhibits myosin light chain phosphatase(MLC phosphatase) by phosphorylating it. MLC phosphataseconverts active myosin light chain (MLC-P) to inactive myosinlight chain (MLC) resulting in relaxtion of the tissue. MLCphosphatase when inhibited increases the gain or sensitivity ofmyosin light chain kinase to calcium. Thus inhibition of MLCphosphatase by ROCK-II enzyme promotes contraction ofsmooth muscle through calcium sensitization (Uehata et al.,1997; Gohla et al., 2000; Somlyo and Somlyo, 2000). In addition,RhoA/Rho-kinase suppresses endothelial nitric oxide synthase(eNOS) inhibiting NO/cGMP pathway involved in relaxation ofcorpus cavernosum smooth muscle (Bivalacqua et al., 2004)
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