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Guanylate
cyclase soluble
subunit beta-2
Guanylate
cyclase soluble
subunit beta-1
Voltage-
dependent
L-type calcium
channel subunit
beta-1
Guanylate
cyclase soluble
subunit alpha-2
Guanylate
cyclase soluble
subunit alpha-3
cGMP-dependent
protein kinase
1
cGMP-dependent
protein kinase
2
Voltage-
dependent
L-type calcium
channel subunit
alpha-1C
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-2
Sarcoplasmic/endoplasmic
reticulum
calcium ATPase
1
Ryanodine
receptor 2
Nitric oxide
synthase,
endothelial
Myosin light
chain kinase,
smooth muscle
Myosin light
chain 3
Myosin LC-P
Myosin light
chain
phosphatase
Calmodulin-1
Calmodulin-1
Calmodulin-1
Calmodulin-1
Potassium
voltage-gated
channel
subfamily D
member 2
Kv channel-
interacting
protein 2
NO
Cyclic GMP
Caffeine
K
+
K
+
Ca
+
Ca
+
Ca
+
Ca
+
Ca
+
Ca
+
NO
GTP
PP
i
L-Arginine
H
+
NADPH
O
2
H
2
O
Citrulline
NADP
Heme
FAD
Flavin
Mononucleotide
Tetrahydrobiopterin
Ca
+
Ca
+
Muscle
Relaxation
Calcium
Magnesium
Manganese
Myosin and actin are unbound
allowing the filaments to
slide further apart,
resulting in muscle
relaxation
Myocyte
Cytosol
The activation of potassium
channels leads to an efflux
of potassium which causes
hyperpolarization of the
myocyte
Smooth muscle relaxation
causes vasodilation of the
arteries and veins
Hyperpolarization
The dephosphoylation of
myosin light
chain-phosphatase causes
myosin to unbind from actin,
causing muscle relaxation.
The low concentration of
calcium means it cannot bind
to calmodulin. This prevents
calmodulin from activating
myosin light chain kinase
which leads to an inhibitory
effect and prevents muscle
contraction.
cGMP-dependent protein
kinase also activates
sarcoplasmic reticulum
calcium ATPase which causes
the reuptake of cytosolic
calcium into the
sarcoplasmic reticulum,
further lowering the
concentration of cytosolic
calcium.
The hyperpolarization of the
muscle cell inhibits
voltage-gates calcium
channels, which are also
inhibited by protein kinase.
This prevents calcium from
entering the myocyte. This
leads to a low concentration
of cytosolic calcium.
Sarcoplasmic Reticulum
Endothelial Cell
Cytosol
Endoplasmic Reticulum
Nitric oxide diffuses
through the layers to the
smooth muscle cells and
activates guanylate cyclase
Caffeine activates Ryanodine
receptors in the endoplasmic
retiuclum of endothelial
cells. This causes calcium
to enter the cytosol.
Calcium binds to calmodulin
which activates nitric oxide
synthase to catalyze the
synthesis of nitric oxide.
Media
The exact mechanism of
caffeine activating
ryanodine receptors is
unknown.
In the head and neck
caffeine reduces the
production of nitric oxide
through antagonism of the
adenosine A2A receptor,
which is known to increase
production of nitric oxide.
Myosin
Actin
Vasodilation
Endoplasmic Reticulum
GUCY1B2
GUCY1B3
CACNB1
GUCY1A2
GUCY1A3
PRKG1
PRKG2
CACNA1C
CACNA2D2
ATP2A1
RYR2
NOS3
MYLK
MYL3
MYL3
PPP1CB
CALM1