Essential Cell Biology 5th edition

G-Protein-Coupled Receptors
555
(A)
smooth muscle cells
lumen of
blood vessel
basal lamina
Figure 16–26 Nitric oxide (NO) triggers smooth muscle relaxation in a bloodvessel
wall. (A) Simplified drawing showing a cross section of a blood vessel with
endothelial cells lining its lumen and smooth muscle cells surrounding the outside
of the vessel. (B) The neurotransmitter acetylcholine causes the blood vessel
to dilate by binding to a GPCR on the surface of the endothelial cells, thereby
activating a G protein, G q , to trigger Ca 2+ release (as illustrated in Figure 16–23).
Ca 2+ activates nitric oxide synthase, stimulating the production of NO. NO then
diffuses out of the endothelial cells and into adjacent smooth muscle cells, where
it regulates the activity of specific proteins, causing the muscle cells to relax. One
key target protein that can be activated by NO in smooth muscle cells is guanylyl
cyclase, which catalyzes the production of cyclic GMP from GTP. Note that NO gas
is highly toxic when inhaled and should not be confused with nitrous oxide (N 2 O),
also known as laughing gas.
endothelial cell
(B)
acetylcholine
activated
NO synthase
(NOS)
NO bound to
guanylyl cyclase
arginine
NO
endothelial cell
IP 3 Ca 2+ ECB5 m15.40-16.26
RAPID DIFFUSION OF NO
ACROSS MEMBRANES
GTP
cyclic
GMP
RAPID RELAXATION
OF SMOOTH MUSCLE CELL
smooth muscle cell
Endothelial cells—the flattened cells that line every blood vessel—release
NO in response to acetylcholine secreted by nearby nerve endings.
Acetylcholine binds to a GPCR on the endothelial cell surface, resulting in
activation of G q and the release of Ca 2+ inside the cell (see Figure 16–23).
Ca 2+ then stimulates nitric oxide synthase, which produces NO from the
amino acid arginine. This NO diffuses into smooth muscle cells in the
adjacent vessel wall, causing the cells to relax; this relaxation allows
the vessel to dilate, so that blood flows through it more freely (Figure
16–26). The effect of NO on blood vessels accounts for the action of nitroglycerin,
which has been used for almost 100 years to treat patients with
angina—pain caused by inadequate blood flow to the heart muscle. In
the body, nitroglycerin is converted to NO, which rapidly relaxes blood
vessels, thereby reducing the workload on the heart and decreasing the
muscle’s need for oxygen-rich blood. Many nerve cells also use NO to
signal neighboring cells: NO released by nerve terminals in the penis,
for instance, acts as a local mediator to trigger the blood-vessel dilation
responsible for penile erection.
Inside many target cells, NO binds to and activates the enzyme guanylyl
cyclase, stimulating the formation of cyclic GMP from the nucleotide GTP
(see Figure 16–26B). Cyclic GMP, a second messenger similar in structure
to cyclic AMP, is a key link in the NO signaling chain. The drug Viagra
enhances penile erection by blocking the enzyme that degrades cyclic
GMP, prolonging the NO signal.
GPCR-Triggered Intracellular Signaling Cascades Can
Achieve Astonishing Speed, Sensitivity, and Adaptability
The steps in the signaling cascades associated with GPCRs take a long time
to describe, but they often take only seconds to execute. Consider how
quickly a thrill can make your heart race (when epinephrine stimulates