CHAPTER 3 • CELLULAR STRUCTURE AND FUNCTION
53
monophosphate (cGMP) via nitric oxide (NO)
activation of guanylyl cyclase (Fig. 3.10).
The IP3 pathway in vascular smooth muscle
is similar to that found in the heart. Norepi-
nephrine and epinephrine (via ^-adrenocep-
tors),
angiotensin
II
(via AT1
receptors),
endothelin-I (via ETA
receptors), vasopressin
(via V1
receptors) and acetylcholine (via M3
receptors) activate phospholipase C through
the Gq-protein, causing the formation of IP3
from PIP2. IP3 then directly stimulates the
sarcoplasmic reticulum to release calcium.
The formation of diacylglycerol from PIP2
activates protein kinase C, which can modu-
late vascular smooth muscle contraction as
well via protein phosphorylation.
Receptors
coupled
to
the
Gs-protein
stimulate adenylyl cyclase, which catalyzes
the formation of cAMP In vascular smooth
muscle, unlike cardiac myocytes, an increase
in cAMP by a ß2-adrenoceptor agonist such
as
isoproterenol
causes
relaxation.
The
mechanism for this process is cAMP inhibi-
tion of myosin light chain kinase (see Fig.
3.9), which decreases myosin light chain
phosphorylation, thereby inhibiting the inter-
actions between actin and myosin. Adenosine
and prostacyclin (PGI2) also activate Gs-pro-
tein through their receptors, leading to an
increase in cAMP and smooth muscle relaxa-
tion. Epinephrine binding to P2-adrenoceptors
relaxes vascular smooth muscle through the
Gs-protein.
A third important mechanism for regulat-
ing vascular smooth muscle contraction is the
NO-cGMP system. Many endothelial-depend-
ent vasodilator substances (e.g., acetylcho-
line, bradykinin, substance P), when bound
to
their
respective
endothelial
receptors,
stimulate
the
conversion
of
L
-arginine
to
NO by activating NO synthase. The NO dif-
fuses from the endothelial cell to the vascular
Epi
Ado
PGI2
■ FIGURE 3.10 Receptors and signal transduction pathways that regulate vascular smooth muscle contrac-
tion.
R,
receptor;
Gs,
stim ulatory G-protein;
Gq,
phospholipase C-coupled G-protein;
AC,
adenylyl cyclase;
PL-C,
phospholipase C;
PIP2,
phosphatidylinositol 4,5-bisphosphate;
IP3,
inositol triphosphate;
DAG,
diacylg-
lycerol;
PK-C,
protein kinase C;
SR,
sarcoplasmic reticulum;
MLCK,
myosin light chain kinase;
Ado,
adeno-
sine;
PGI2,
prostacyclin;
Epi,
epinephrine;
NO,
nitric oxide;
GC,
guanylyl cyclase;
AII,
angiotensin II;
ET-1,
endothelin-1;
NE,
norepinephrine;
ACh,
acetylcholine;
AVP,
arginine vasopressin;
GDP,
guanosine diphos-
phate;
GTP,
guanosine triphosphate;
ATP,
adenosine triphosphate;
cAMP,
cyclic adenosine monophosphate;
cGMP
, cyclic guanosine monophosphate.
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