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Well-established
that cAMP and cGMP decreases Ca2+ sensitivity of
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contraction in
both intact and permeabilized smooth muscle.
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In vitro, PKA
phosphorylates MLCK at two sites; site A decreases
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affinity of MLCK
for Ca2+/calmodulin complex.
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However, agents
that elevate PKA have negligible effects on
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phosphorylation
of site A and Ca2+ activation of MLCK; suggests that
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cAMP/PKA
desensitizes smooth muscle by an alternate mechanism.
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Phosphorylation
of MLCK by PKG has no effect on activity.
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Endogenous nitric
oxide and related nitrovasodilators regulate blood
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pressure by
activation of soluble guanylate cyclase, elevation of cGMP,
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activation of
cGMP dependent kinase (cGKIaor PKG). cGMP-mediated
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vascular smooth
muscle cell relaxation is characterized by a reduction in
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intracellular
calcium concentration and activation of PP1M, which
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reduces the
sensitivity of the contractile apparatus to intracellular calcium.
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The mechanism by
which cGMP increases PP1M activity and myosin
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light chain
dephosphorylation was elucidated in a series of experiments
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published by Surks et al.
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