Nitric oxide (NOS) signaling

–– Nitric oxide (NO) is synthesized by nitric oxide synthase (NOS), which oxidizes a guanidine nitrogen of L-arginine
releasing NO in the form of a free radical and citrulline.

–– Three isoforms of NOS have been identified: endothelial (eNOS or NOS-3), neuronal (nNOS or NOS-1), and
inducible (iNOS or NOS-2), each with separate functions.

–– NO acts as a messenger in diverse functions including vasodilation, neurotransmission, anti-tumor and anti-
pathogenic activities, but sustained levels of NO production result in direct tissue toxicity, septic shock,
carcinomas and inflammatory conditions.

Inducible NOS (iNOS, NOS2) signaling

Inflammation
T-tubule
beta-AR
Increased cAMP
hydrolysis NOS2
ICa XO
(INOS)
PDE2 PDE5
Ca channel
Caveolae
NADPH
NO O2-
ICa oxidase
P
sGC Ca2+
P ONOO

PKG RyR
cGMP
PLB
SR
Ca 2+
Decrease Ca2 sensitivity and
Cell damage
myofilament contractility SERCA

Endothelial NOS (eNOS, NOS3) signaling

T-tubule
beta-AR

Iks P
SOD NO PDE5
K sGC Ca2+
Caveolae channel
Caveolin-3
ICa RyR
Ca P
NOS3 channel
(eNOS) P PKG SR
cGMP
P
PTEN P13K βγ α
P P
Akt PDK1/2 P G-PCR
Decrease Ca2 sensitivity and
P P P
myofilament contractility P P
PIP3 P PIP3 P PIP2 P
RTK

Neuronal NOS (nNOS, NOS1) signaling

T-tubule

Ca channel
P
ICa Calcineurin NF-AT
ONOO
S-nitrosylation
Caveolae P

NO
O2- NO
ICa NF-AT
P
Ca2+
P XO Nuclear gene
NOS1 targets
sGC RyR
(nNOS)
cGMP PLB Ca2+

PKG Ca2+ SR NOS1

Decrease Ca2 sensitivity and (nNOS)
myofilament contractility SERCA

Find out more at www.abcam.com/NOS