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Gq protein
signaling
cascade
Phospholipase C
Inositol 1,4,5-
trisphosphate
receptor type 1
Protein kinase
C alpha type
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
Myosin light
chain kinase,
smooth muscle
cAMP-dependent
protein kinase
catalytic
subunit alpha
cAMP-dependent
protein kinase
catalytic
subunit beta
cAMP-dependent
protein kinase
type I-alpha
regulatory
subunit
cAMP-dependent
protein kinase
catalytic
subunit gamma
cAMP-dependent
protein kinase
type I-beta
regulatory
subunit
cAMP-dependent
protein kinase
type II-beta
regulatory
subunit
cAMP-dependent
protein kinase
type II-alpha
regulatory
subunit
D(1A) dopamine
receptor
Adenylate
cyclase type 2
Guanine
nucleotide-
binding protein
G(s) subunit
alpha isoforms
short
Myosin LC-P
Myosin light
chain 3
Calmodulin-1
Myosin light
chain
phosphatase
Calmodulin-1
Inositol 1,4,5-trisphosphate
Fenoldopam
Ca
+
Ca
+
Ca
+
Fenoldopam
Phosphatidylinositol
4,5-bisphosphate
ATP
cAMP
PP
i
ATP
Calcium
Guanosine
triphosphate
Magnesium
Ca
+
Diacylglycerol
Muscle
Contraction
Muscle
Relaxation
Magnesium
Calcium
Manganese
Sarcoplasmic Reticulum
Cross-bridge formation
between myosin and actin
does not occur, since myosin
cannot undergo
phosphorylation by MLCK
Decreased calcium is unable
to bind readily to
calmodulin so it does not
activate myosin light chain
kinase
Activation of myosin light
chain kinase leading to high
concentration of myosin LC-P
There is an overall decrease
in calcium levels in the
cytosol caused by the
inhibition of the Gq
signaling cascade
Cytosol
Smooth Muscle Myocyte
Dopamine receptors (D1 and
D5) located in the tunica
media of the artery exert
their effect through G-alpha
stimulatory second messenger
system
Actin
Myosin
Fenoldopam is administered
as a continuous intravenous
infusion using an infusion
pump
In the cell, cAMP activates
protein kinase A (PKA) which
in turn phosphorylates MLCK,
causing its inactivation
The result of relation is
the dilation of arteries
producing decreased systemic
vascular resistance (SVR),
increased renal blood flow,
natriuresis, and diuresis,
thus a decrease in blood
pressure.
Artery
Upon ligand binding to
D1-receptors, the alpha
subunit dissociates from the
intracellular domain of the
transmembrane receptor and
activates adenylate cyclase
(AC). AC subsequently
converts ATP to cyclic
adenosine monophosphate
(cAMP)
GNAQ
PLCB1
ITPR1
PRKCA
CACNA1A
CACNB1
CACNA2D2
MYLK
PRKACA
PRKACB
PRKAR1A
PRKACG
PRKAR1B
PRKAR2B
PRKAR2A
DRD1
ADCY2
GNAS
MYL3
MYL3
CALM1
PPP1CB
CALM1
Inositol 1,4,5-
trisphosphate
Fenoldopam
Calcium
Calcium
Calcium
Fenoldopam
Phosphatidylinositol
4,5-
bisphosphate
Adenosine
triphosphate
cAMP
Pyrophosphate
Adenosine
triphosphate
Calcium
Diacylglycerol
Muscle
Contraction
Muscle
Relaxation