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Beta-endorphin
Adenylate
cyclase type 2
Serine/threonine-
protein
phosphatase
PP1-beta
catalytic
subunit
Voltage-
dependent
L-type calcium
channel subunit
beta-1
G protein-
activated
inward
rectifier
potassium
channel 3
Myosin light
chain 3
Myosin light
chain 3
Mu-type opioid
receptor
Gβ
Gγ
Neuronal
acetylcholine
receptor
subunit beta-2
NO
Acetylcholine
Naldemedine
Na
+
NO
NO
Acetylcholine
Na
+
Ca
+
Ca
+
Na
+
Na
+
ATP
cAMP
PP
i
Naldemedine
GTP
Neuronal
acetylcholine
receptor
subunit alpha-4
Muscle
Relaxation
nAchR Smooth
Muscle
Contraction
Guanine
nucleotide-
binding protein
G(i) subunit
alpha-1
Magnesium
Manganese
More ACh leads to stimule
all three types of
contractions of the smooth
muscle cells of the GI
tract.
Neuromuscular Junction
Increased calcium levels
lead to increased
neurotransmitter release. NO
is released by synaptic
vesicles in inhibitory
motorneurones.
NO relaxes the smooth muscle
cells of the GI tract.
The rythmic action of the
neurotransmitters creates
the peristalsis and the good
GI transit.
Smooth Muscle Myocyte
Increased calcium levels
lead to increased
neurotransmitter release.
Acetylcholine is released by
synaptic vesicles.
Naldemedine prevents the
gamma subunit of the mu
opioid receptor from
inhibiting the N-type
calcium channels on the
neuron. This allows calcium
to enter the neuron and
depolarize.
The inhibition of Mu-type
opioid receptors prevents
the Gi subunit of the mu
opioid receptor from
activating the outward
rectifying sodium channel.
This prevents
hyperpolarization
Pre-Synaptic Neuron
Cytosol
Synaptic Vesicle
With the mu opioid receptor
unable to inhibit adenylate
cyclase, it is able to
synthesize cAMP which
increases the excitability
of the neuron leading to
neurotransmitter release
Synaptic Vesicle
Unknown
ADCY2
PPP1CB
CACNB1
KCNJ9
MYL3
MYL3
OPRM1
GNB1
GNG2
Unknown
Nitric oxide
Acetylcholine
Naldemedine
Sodium
Nitric oxide
Nitric oxide
Acetylcholine
Sodium
Calcium
Calcium
Sodium
Sodium
Adenosine
triphosphate
cAMP
Pyrophosphate
Naldemedine
Guanosine
triphosphate
Unknown
Muscle
Relaxation
nAchR Smooth
Muscle
Contraction
GNAI1