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Myosin light
chain kinase,
smooth muscle
PKA complex
PKA complex
Guanine
nucleotide-
binding protein
G(s) subunit
alpha isoforms
short
5-
hydroxytryptamine
receptor 4
Myosin LC-P
Myosin light
chain 3
Voltage-
dependent
L-type calcium
channel subunit
beta-1
Voltage-
dependent
L-type calcium
channel subunit
alpha-1C
Myosin light
chain
phosphatase
Calmodulin
Intermediate
conductance
calcium-
activated
potassium
channel protein
4
Adenylate
cyclase type 5
Calmodulin
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-1
Prucalopride
Ca
+
K
+
K
+
Ca
+
GDP
GTP
ATP
cAMP
PP
i
P
i
P
i
Ca
+
Muscle
Contraction
Muscle
Relaxation
Magnesium
Calcium
Manganese
Cytosol
Smooth Muscle Myocyte
The G protein complex
separates into alpha and
beta/gamma subunits.
GDP is replaced with GTP on
the alpha subunit.
Activated PKA can
phosphorylate calcium
activated potassium channels
causing potassium efflux and
promoting hyperpolarization.
High PKA activity leads to
increased phosphorylation of
certain proteins, including
myosin light chain (MLC), in
smooth muscle cells.
Increased MLC
phosphorylation promotes the
activation of myosin light
chain kinase (MLCK).
There is an overall increase
in calcium levels in the
cytosol.
Increased calcium is able to
bind readily to calmodulin.
The activation of myosin
light chain kinase activates
the synthesis of Myosin LC-P
which leads to a high
concentration of myosin
light chain and muscle
contraction
Myosin binds from actin
causing sarcomere filaments
to slide resulting in muscle
contraction
Actin
Myosin
Prucalopride binds to 5-HT 4
receptors that activate Gs
signalling to cause smooth
muscle contraction in the
gastrointestinal tract.
Prucalopride is administered
orally
As cAMP levels increase, the
levels of phosphorylated
proteins involved in
contraction increase,
leading to higher
intracellular calcium
concentration.
Gastrointestinal tract
blood vessel
MYLK
PRKAR1A
PRKAR2A
GNAS
HTR4
MYL3
MYL3
CACNB1
CACNA1C
PPP1CB
CALM1
KCNN4
ADCY5
CALM1
CACNA2D1
Prucalopride
Calcium
Potassium
Potassium
Calcium
Guanosine
diphosphate
Guanosine
triphosphate
Adenosine
triphosphate
cAMP
Pyrophosphate
Phosphate
Phosphate
Calcium
Muscle
Contraction
Muscle
Relaxation