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Adenylate
cyclase type 10
Myosin light
chain kinase,
smooth muscle
PKA complex
PKA complex
Protein kinase
C
D(2) dopamine
receptor
D(2) dopamine
receptor
Myosin LC-P
Myosin light
chain 3
Inositol 1,4,5-
trisphosphate
receptor type 1
Voltage-
dependent
L-type calcium
channel subunit
beta-1
Voltage-
dependent
L-type calcium
channel subunit
alpha-1C
Voltage-
dependent
P/Q-type
calcium channel
subunit
alpha-1A
Voltage-
dependent
L-type calcium
channel subunit
beta-1
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-2
Sodium-
dependent
dopamine
transporter
Synaptic
vesicular amine
transporter
Myosin light
chain
phosphatase
Calmodulin
Intermediate
conductance
calcium-
activated
potassium
channel protein
4
Phospholipase C
ATP-binding
cassette
sub-family C
member 8
ATP-sensitive
inward
rectifier
potassium
channel 8
ATP-sensitive
inward
rectifier
potassium
channel 11
ATP-binding
cassette
sub-family C
member 9
Aromatic-L-
amino-acid
decarboxylase
Tyrosine
3-monooxygenase
Calmodulin
Voltage-
dependent
calcium channel
subunit
alpha-2/delta-1
Dopamine
Ca
+
Domperidone
Ca
+
Ca
+
K
+
K
+
Ca
+
K
+
K
+
Ca
+
Dopamine
Dopamine
Domperidone
ATP
cAMP
Inositol 1,4,5-trisphosphate
Phosphatidylinositol
4,5-bisphosphate
Diacylglycerol
L-Dopa
CO
2
L-Tyrosine
Tetrahydrobiopterin
O
2
Dihydrobiopterin
H
2
O
Na
+
Na
+
P
i
P
i
P
i
P
i
Calcium
Pyridoxal
5'-phosphate
Ca
+
Muscle
Contraction
Muscle
Relaxation
Gi Signaling
Cascade
Gi Protein
Signaling
Cascade
Magnesium
Calcium
Fe2+
Manganese
Sarcoplasmic Reticulum
Cytosol
Stomach Smooth Muscle Cell
Activated PKA can
phosphorylate calcium
activated potassium channels
causing potassium efflux and
promoting hyperpolarization.
Activated PKA phosphorylates
the IP3 receptor to reduce
its affinity for IP3.
Activated PKA phosphorylates
phospholipase C.
There is an overall decrease
in calcium levels in the
cytosol.
Decreased calcium is unable
to bind readily to
calmodulin.
The inhibition of myosin
light chain kinase prevents
the synthesis of Myosin LC-P
which leads to a high
concentration of myosin
light chain and muscle
relaxation.
Myosin binds to actin
causing the sarcomere
filaments to key into each
other resulting in muscle
contractility.
Activates ATP-sensitive
potassium channels via cAMP
mediated phosphorylation.
Actin Filament
Myosin Filament
Since the receptor isn't
activated, adenylyl cyclase
is no longer inhibited
allowing for cAMP production
D2 receptors activate Gi
protein signalling which
inhibits adenylyl cyclase
Cytosol
Postsynaptic Neuron
Presynaptic Neuron
Cytosol
Synaptic Vesicle
Synapse
Domperidone is a prokinetic
agent. It increases gastric
motility and increases the
release of ACh from the GI
tract
↓ nausea and vomiting
Brain
Blood vessel
passive diffusion
Dopamine receptors in the
chemoreceptor trigger zone
(area postrema) is
stimulated to cause nausea
and vomiting
Domperidone acts as an
antagonist to D2 receptors
present in the vagus nerves
from brain to gut
Vomiting Centre (medulla)
Chemoreceptor trigger zone
Domperidone blocks dopamine
receptors in the
chemoreceptor trigger zone