448
P A R T 5
Drugs acting on the autonomic nervous system
building blocks necessary to produce noradrenaline (see
Figure 29.4).
Noradrenaline release
When the nerve is stimulated, the action potential travels
down the nerve axon and arrives at the axon terminal
(see Chapter 19). The action potential then depolarises
the axon membrane. This action allows calcium into the
nerve, causing the membrane to contract and the storage
vesicles to fuse with the cell membrane, releasing their
load of noradrenaline into the synaptic gap or cleft. The
noradrenaline travels across the very short gap to very
specific adrenergic receptor sites on the effector cell on
the other side of the synaptic gap.
Adrenergic receptors
Adrenergic receptors
can be stimulated by the neuro-
transmitter released from the axon in the immediate
vicinity and they can be further stimulated by circulat-
ing noradrenaline and adrenaline secreted directly into
the bloodstream by the adrenal medulla. The receptor
sites that react with neurotransmitters at adrenergic
sites have been classified as
alpha-receptors
and
beta-
receptors
. These receptors are further classified as
alpha
1
(
a
1
)-, alpha
2
(
a
2
)-, beta
1
(
b
1
)- and beta
2
(
b
2
)-
receptors (see Table 29.2). It is thought that receptors
may respond to different concentrations of noradrena-
line or different ratios of noradrenaline and adrenaline.
Different drugs that are known to affect the SNS may
affect parts of the sympathetic response, but not all of
it, because they are designed to stimulate specific adren-
ergic receptors.
Alpha-receptors
Alpha
1
-receptors are found in blood vessels, in the iris
and in the urinary bladder. In blood vessels, they can
cause vasoconstriction and increase peripheral resist-
ance, thus raising blood pressure. In the iris, they cause
pupil dilation. In the urinary bladder, they cause the
increased closure of the internal sphincter.
Alpha
2
-receptors are located on nerve mem-
branes and act as modulators of noradrenaline release.
When noradrenaline is released from a nerve ending,
it crosses the synaptic cleft to react with its specific
receptor site. Some of it also flows back to react with
the alpha-receptor on the nerve membrane. This causes
a reflex decrease in noradrenaline release. In this way,
the alpha
2
-receptor helps to prevent overstimulation of
effector sites. These receptors are also found on the beta
cells in the pancreas, where they help to moderate the
insulin release stimulated by SNS activation.
Beta-receptors
Beta
1
-receptors are found in cardiac tissue, where they
can stimulate increasedmyocardial activity and increased
heart rate. They are also responsible for increased
lipolysis or breakdown of fat for energy in peripheral
tissues. Beta
2
-receptors are found in the smooth muscle
in blood vessels, in the bronchi, in the periphery and in
uterine muscle. In blood vessels, beta
2
stimulation leads
to vasodilation. Beta
2
-receptors also cause dilation in
the bronchi. In the periphery, they can cause increased
muscle and liver breakdown of glycogen and increased
release of glucagon from the alpha cells of the pancreas.
Stimulation of beta
2
-receptors in the uterus results in
relaxed uterine smooth muscle.
The sympathetic response
Perception of stress—Limbic system
Hypothalamus
ACTH
TSH
↑
Thyroid levels
↑
Metabolism
Cortisol
↓
immune function
↓
inflammatory response
↑
glucose levels
Aldosterone
↑
Na
+
retention
↑
water retention
↓
K
+
↑
blood volume
↑
ADH release
↑
water retention
SNS
•
↑
BP
•
↑
P
•
↑
heart contraction
•
↑
R
• bronchodilation
• pupil dilation
• sweating
• piloerection
• glycogenolysis
• blood to muscle
• sphincter constriction
• blood directed away
from organs
•
↓
GI activity and
secretions
↑
aldosterone
↑
BP
renin-angiotensin
system activated
FIGURE 29.3
The “fight-or-flight” response:
the sympathetic stress reaction. ACTH,
adrenocorticotropic hormone; ADH,
antidiuretic hormone; BP, blood pressure;
GI, gastrointestinal; P, pulse; R, respiratory
rate; SNS, sympathetic nervous system;
TSH, thyroid-stimulating hormone.
