pham ANS PHARMA.ppt

Copyright © 2010 Pearson Education, Inc.
Nervous System Overview
• Nervous System
• Brain
• Spinal cord
• Nerves
• Functions of nervous system
• Regulates and coordinates all body activities
• Center of all mental activity, including thought,
learning, and memory

Nervous System Divisions
• Central Nervous System (CNS)
• Brain
• Spinal Cord
• Processes and stores sensory and motor information
• Controls consciousness
• Peripheral Nervous System (PNS)
• 12 Pairs of Cranial Nerves
• 31 Pairs of Spinal Nerves
• Transmits sensory and motor impulses back and forth
between CNS and rest of body

Peripheral Nervous System
• Somatic Nervous System (SNS)
• Provides voluntary control over skeletal
muscle contractions
• Autonomic Nervous System (ANS)
• Provides involuntary control over smooth
muscle, cardiac muscle, and glandular
activity and secretions in response to the
commands of the central nervous system

Autonomic Nervous System
• Sympathetic nerves
• Increase heart rate
• Constrict blood vessels
• Raise blood pressure
• Fight-or-flight response
• Parasympathetic nerves
• Slow heart rate
• Increase peristalsis of intestines
• Increase glandular secretions
• Relax sphincters

Autonomic Nervous System (ANS)
• The ANS consists of motor neurons that:
• Innervate smooth and cardiac muscle and
glands
• Make adjustments to ensure optimal support
for body activities
• Operate via subconscious control

Autonomic Nervous System (ANS)
• Other names
• Involuntary nervous system
• General visceral motor system

Central nervous system (CNS) Peripheral nervous system (PNS)
Motor (efferent) division
Sensory (afferent)
division
Somatic nervous
system
Autonomic nervous
system (ANS)
Sympathetic
division
Parasympathetic
division
Figure 14.1

Somatic and Autonomic Nervous Systems
• The two systems differ in
• Effectors
• Efferent pathways (and their
neurotransmitters)
• Target organ responses to neurotransmitters

Effectors
• Somatic nervous system
• Skeletal muscles
• ANS
• Cardiac muscle
• Smooth muscle
• Glands

Efferent Pathways
• A, thick, heavily myelinated somatic motor fiber makes
up each pathway from the CNS to the muscle
• ANS pathway is a two-neuron chain
1. Preganglionic neuron (in CNS) has a thin, lightly
myelinated preganglionic axon
2. Ganglionic neuron in autonomic ganglion has an
unmyelinated postganglionic axon that extends to the
effector organ

Neurotransmitter Effects
• All somatic motor neurons release acetylcholine (ACh)
• Effects are always stimulatory
• ANS
• Preganglionic fibers release ACh
• Postganglionic fibers release norepinephrine or ACh at
effectors
• Effect is either stimulatory or inhibitory, depending on
type of receptors

Catecholamines
• Substances that can produce a sympathomimetic
response
1. Endogenous:
Dopamine (Dopaminergic) epinephrine & norepinephrine
(Adrenegeric)
2. Synthetic:
isoproterenol, dobutamine, phenylephrine

Skeletal muscle
Cell bodies in central
nervous system Peripheral nervous system Effect
+
+
Effector
organs
ACh
ACh
Smooth muscle
(e.g., in gut),
glands, cardiac
muscle
Ganglion
Adrenal medulla Blood vessel
ACh
ACh
ACh
NE
Epinephrine and
norepinephrine
Acetylcholine (ACh) Norepinephrine (NE)
Ganglion
Heavily myelinated axon
Lightly myelinated
preganglionic axon
Lightly myelinated
preganglionic axons
Neuro-
transmitter
at effector
Unmyelinated
postganglionic
axon
Unmyelinated
postganglionic axon
Stimulatory
Stimulatory
or inhibitory,
depending
on neuro-
transmitter
and
receptors
on effector
organs
Single neuron from CNS to effector organs
Two-neuron chain from CNS to effector organs
SOMATIC
NERVOUS
SYSTEM
AUTONOMIC
NERVOUS
SYSTEM
PARASYMPATHETIC
SYMPATHETIC
Figure 14.2

Divisions of the ANS
1.Sympathetic division
2.Parasympathetic division
• Dual innervation
• Almost all visceral organs are served by both
divisions, but they cause opposite effects

Role of the Parasympathetic Division
• Promotes maintenance activities and
conserves body energy
• Its activity is illustrated in a person who
relaxes, reading, after a meal
• Blood pressure, heart rate, and respiratory
rates are low
• Gastrointestinal tract activity is high
• Pupils are constricted and lenses are
accommodated for close vision

Role of the Sympathetic Division
• Mobilizes the body during activity; is the “fight-
or-flight” system
• Promotes adjustments during exercise, or
when threatened
• Blood flow is shunted to skeletal muscles and
heart
• Bronchioles dilate
• Liver releases glucose

Division
Origin of
Fibers
Length of
Fibers
Location
of Ganglia
Sympathetic Thoracolumbar
region of the
spinal cord
Short
preganglionic
and long
postganglionic
Close to
spinal cord
Parasympathetic Brain and
sacral spinal
cord
(craniosacral)
Long
preganglionic
and short
postganglionic
In v isceral
effector
organs
ANS Anatomy

Salivary
glands
Eye
Skin*
Heart
Lungs
Liver
and gall-
bladder
Genitals
Pancreas
Eye
Lungs
Bladder
Liver and
gall-
bladder
Pancreas
Stomach
Cervical
Sympathetic
ganglia
Cranial
Lumbar
Thoracic
Genitals
Heart
Salivary
glands
Stomach
Bladder
Adrenal
gland
Parasympathetic Sympathetic
Sacral
Brain
stem
L1
T1
Figure 14.3

Cranial Nerve Ganglia
(Terminal Ganglia)
Effector Organ(s)
Oculomotor (III) Ciliary Eye
Facial (VII) Pterygopalatine
Submandibular
Salivary, nasal, and
lacrimal glands
Glossopharyngeal
(IX)
Otic Parotid salivary glands
Cranial
Outflow
Vagus (X) Within the walls of
target organs
Heart, lungs, and most
visceral organs
Sacral
Outflow
S2-S4
Within the walls of
target organs
Large intestine,
urinary bladder,
ureters, and
reproductive organs
Parasympathetic (Craniosacral) Division
Outflow

Pterygopalatine
ganglion
Eye
Lacrimal
gland
Nasal
mucosa
Ciliary
ganglion
Pterygopalatine
ganglion
Submandibular
ganglion Submandibular
and sublingual
glands
CN III
CN VII
CN IX
CN X
Otic ganglion
Parotid gland
Heart
Lung
Liver and
gallbladder
Stomach
Pancreas
Urinary
bladder
and ureters
Small
intestine
Large
intestine
S2
Pelvic
splanchnic
nerves
Genitalia
(penis,
clitoris, and vagina)
Rectum
Celiac
plexus
Inferior
hypogastric
plexus
Cardiac and
pulmonary
plexuses
S4
Preganglionic
Postganglionic
Cranial nerve
Figure 14.4

Sympathetic (Thoracolumbar) Division
• Preganglionic neurons are in spinal cord
segments T1 – L2
• Sympathetic neurons produce the lateral
horns of the spinal cord
• Preganglionic fibers pass through the white
rami communicantes and enter sympathetic
trunk (paravertebral) ganglia

Copyright © 2010 Pearson Education, Inc. Figure 14.6
Superior
cervical
ganglion
Middle
cervical
ganglion
Inferior
cervical
ganglion
Sympathetic trunk
(chain) ganglia
Pons
L2
T1
White rami
communicantes
Liver and
gallbladder
Stomach
Spleen
Kidney
Adrenal medulla
Small
intestine
Large
intestine
Genitalia (uterus, vagina, and
penis) and urinary bladder
Celiac ganglion
Inferior
mesenteric
ganglion
Lesser splanchnic nerve
Greater splanchnic nerve
Superior
mesenteric
ganglion
Lumbar
splanchnic
nerves
Eye
Lacrimal gland
Nasal mucosa
Blood vessels;
skin (arrector pili
muscles and
sweat glands)
Salivary glands
Heart
Lung
Rectum
Cardiac and
pulmonary
plexuses
Preganglionic
Postganglionic
Sacral
splanchnic
nerves

Sympathetic Trunks and Pathways
• There are 23 paravertebral ganglia in the
sympathetic trunk (chain)
• 3 cervical
• 11 thoracic
• 4 lumbar
• 4 sacral
• 1 coccygeal

Heart
Lungs and
diaphragm
Liver
Stomach
Kidneys
Ovaries
Small intestine
Ureters
Urinary
bladder
Colon
Pancreas
Liver
Heart
Appendix
Gallbladder

Neurotransmitters
• Cholinergic fibers release the neurotransmitter ACh
• All ANS preganglionic axons
• All parasympathetic postganglionic axons
• Adrenergic fibers release the neurotransmitter NE
• Most sympathetic postganglionic axons
• Exceptions: sympathetic postganglionic fibers secrete
ACh at sweat glands and some blood vessels in
skeletal muscles

Major Neurotransmitters
•Acetylcholine
•GABA
•Dopamine
•Epinephrine
•Serotonin

• Acetylcholine (ACh)
• Smooth muscle, cardiac muscle, and
exocrine glands
• Anticholinergics block ACh receptors
• GABA
• Dopamine
• Epinephrine
• Serotonin

• Acetylcholine
•GABA (gamma-aminobutyric acid)
Regulates message delivery system
of the brain
• Dopamine
• Epinephrine
• Serotonin

• Acetylcholine
• GABA
•Dopamine
Acts on the CNS and kidneys
• Epinephrine
• Serotonin

• Acetylcholine
• GABA
• Dopamine
•Epinephrine
• Acts on cardiac and bronchodilator
receptors
• Known as Adrenaline
• Serotonin

• Acetylcholine
• GABA
• Dopamine
• Epinephrine
• Serotonin
• Acts on smooth muscle and gastric
mucosa (causes vasoconstriction)
• Emotional responses: depression,

+
ACh
Smooth muscle
(e.g., in gut),
glands, cardiac
muscle
Ganglion
Adrenal medulla Blood vessel
ACh
ACh
ACh
NE
Epinephrine and
norepinephrine
Acetylcholine (ACh) Norepinephrine (NE)
Ganglion
Lightly myelinated
preganglionic axon
Lightly myelinated
preganglionic axons
Unmyelinated
postganglionic
axon
Unmyelinated
postganglionic axon
Stimulatory
or inhibitory,
depending
on neuro-
transmitter
and
receptors
on effector
organs
Two-neuron chain from CNS to effector organs
AUTONOMIC
NERVOUS
SYSTEM
PARASYMPATHETIC
SYMPATHETIC

Synapse:
It is the junction of
nerve terminal with the
next neuron or effector
cell, consisting of
presynaptic membrane,
postsynaptic
membrane and
synaptic space.
pre post
Chemical Transmission in Autonomic NS
Transmitter:
It is the chemical agent
released from nerve
terminal that transmits
information across
synapse and to
effectors.
Synapse
西安交大医学院药理学系曹永孝 yxy@xjtu.edu.cn; 029-82655140

Action potential（AP
）passing down an
axon to the axon
terminal changes
membrane
polarization
resulting in Ca2+
entry into the
cell.
This triggers the fusion of
vesicles containing
neurotransmitters and cell
membrane, and causes the
release of neurochemical
(neurotransmitter) into the
synaptic cleft.
The transmitters diffuse
across the cleft and bind to
receptors on the
postsynaptic membrane to
induce a response in the
postsynaptic neuron.
Chemical Transmission in synapse

Cholinergic
Transmission Choline is
transported into
the presynaptic
nerve terminal
by a carrier (A)
Once synthesized,
ACh is transported
into and packaged
in the vesicles.
ACh is
synthesized
from acetyl
coenzyme A
(Ac-CoA) and
choline
through the
catalytic action
of choline
acetyl
transferase
(ChAT).

Cholinergic
Transmission
After release,
ACh bind to
and activate
pre- and
postsynaptic
acetylcholine
receptors
(cholinoceptor
), showing the
action of
transmitter.
Then, ACh is
hydrolyzed rapidly
by acetylcholin-
esterase (AChE),
terminating the
action of the
transmitter.
When an AP reaches the
terminal and triggers
influx of Ca2+ which
facilitates the fusion of
the vesicular membrane
with the terminal
membrane and results in
the release of ACh into
synaptic space.

Cholinergic
Transmissio
n
• Fig. Action potential-
induced release of the
neurotransmitter
acetylcholine (ACh)
and its metabolism at
the neuromuscular
junction.

Copyright © 2010 Pearson Education, Inc. 西安交大医学院药理学系曹永孝 yxy@xjtu.edu.cn; 029-82655140
.
Tyrosine is transported
actively into the
noradrenergic ending
and is converted to
dopa by tyrosine
hydroxylase
Dopa is
decarboxylated to
dopamine by dopa
decarboxylase.
Dopamine is
transported into the
vesicles and then
converted to NE by
dopamine-beta-
hydroxylase. In the
adrenal medulla, NE is
further converted to
Adrenergic Transmission
Norepinephrine,NE

.
An action potential
causes an influx of Ca2+
into the nerve terminal,
fusion of the vesicle
with the plasma
membrane and
exocytosis of NE.
The transmitter
then activates
receptors in the
postsynaptic
membrane.

.
NE in the synaptic
space is actively
reuptaken into the
nerve and the storage
vesicles (uptake l). It
is the most important
mechanism for
termination of the
action.
NE penetrates into
smooth cells (uptake 2)
and diffuses away
from the receptor site,
is inactivated by
COMT (enzyme) to
normetanephrine
(NMN).

2．NA的合成、释放与灭活：主要在神经末梢合成
合成：酪氨酸从血进人神经元多巴多巴胺 NA
贮存：合成的NA与 ATP和嗜铬颗粒蛋白结合贮存于囊泡中。
释放：
神经冲动到达
前膜，
NA胞裂外排进
入突触间隙，与受
体结合产生效应
终止：
突触间隙中的
NA
大部分被再摄
入神
酪氨酸
羟化酶
多巴
脱羧酶
多巴胺
β-羟化酶
Another portion of the NE
reuptaken into the nerve is
deaminated by MAO enzyme.
NE can also
activate
presynaptic (α2)
receptors, to
inhibit further
release of NE.

Receptors for Neurotransmitters
1.Cholinergic receptors for ACh
2.Adrenergic receptors for NE

Cholinergic Receptors
• Two types of receptors bind ACh
1.Nicotinic
2.Muscarinic
• Named after drugs that bind to them and
mimic ACh effects

Nicotinic Receptors
• Found on
• Motor end plates of skeletal muscle cells
(Chapter 9)
• All ganglionic neurons (sympathetic and
parasympathetic)
• Hormone-producing cells of the adrenal
medulla
• Effect of ACh at nicotinic receptors is always
stimulatory

Muscarinic Receptors
• Found on
• All effector cells stimulated by postganglionic
cholinergic fibers
• The effect of ACh at muscarinic receptors
• Can be either inhibitory or excitatory
• Depends on the receptor type of the target
organ

1 Cholinoceptors :
The receptors combined with ACh are classified as
muscarinic and nicotinic receptors.

Adrenergic Receptors
• Two types
• Alpha () (subtypes 1, 2)
• Beta () (subtypes 1, 2 , 3)
• Effects of NE depend on which subclass of
receptor predominates on the target organ

2 Adrenoceptors:
The receptors combined with NE and adrenaline include
two groups

Effects of Drugs
• Atropine
• Anticholinergic; blocks muscarinic receptors
• Used to prevent salivation during surgery, and
to dilate the pupils for examination
• Neostigmine
• Inhibits acetylcholinesterase
• Used to treat myasthenia gravis

Effects of Drugs
• Over-the-counter drugs for colds, allergies,
and nasal congestion
• Stimulate -adrenergic receptors
• Beta-blockers
• Drugs that attach to 2 receptors to dilate lung
bronchioles in asthmatics; other uses

Interactions of the Autonomic Divisions
• Most visceral organs have dual innervation
• Dynamic antagonism allows for precise
control of visceral activity
• Sympathetic division increases heart and
respiratory rates, and inhibits digestion and
elimination
• Parasympathetic division decreases heart and
respiratory rates, and allows for digestion and
the discarding of wastes

Sympathetic Tone
• Sympathetic division controls blood pressure,
even at rest
• Sympathetic tone (vasomotor tone)
• Keeps the blood vessels in a continual state of
partial constriction

Sympathetic Tone
• Sympathetic fibers fire more rapidly to
constrict blood vessels and cause blood
pressure to rise
• Sympathetic fibers fire less rapidly to prompt
vessels to dilate to decrease blood pressure
• Alpha-blocker drugs interfere with vasomotor
fibers and are used to treat hypertension

Parasympathetic Tone
• Parasympathetic division normally dominates the
heart and smooth muscle of digestive and urinary
tract organs
• Slows the heart
• Dictates normal activity levels of the digestive and
urinary tracts
• The sympathetic division can override these effects
during times of stress
• Drugs that block parasympathetic responses
increase heart rate and block fecal and urinary
retention

Cooperative Effects
• Best seen in control of the external genitalia
• Parasympathetic fibers cause vasodilation;
are responsible for erection of the penis or
clitoris
• Sympathetic fibers cause ejaculation of
semen in males and reflex contraction of a
female’s vagina

Unique Roles of the Sympathetic Division
• The adrenal medulla, sweat glands, arrector pili
muscles, kidneys, and most blood vessels receive
only sympathetic fibers
• The sympathetic division controls
• Thermoregulatory responses to heat
• Release of renin from the kidneys
• Metabolic effects
• Increases metabolic rates of cells
• Raises blood glucose levels
• Mobilizes fats for use as fuels

Localized Versus Diffuse Effects
• Parasympathetic division: short-lived, highly
localized control over effectors
• Sympathetic division: long-lasting, bodywide
effects

Effects of Sympathetic Activation
• Sympathetic activation is long lasting because
NE
• Is inactivated more slowly than ACh
• NE and epinephrine are released into the
blood and remain there until destroyed by the
liver

Control of ANS Functioning
• Hypothalamus—main integrative center of
ANS activity
• Subconscious cerebral input via limbic lobe
connections influences hypothalamic function
• Other controls come from the cerebral cortex,
the reticular formation, and the spinal cord

Cerebral cortex
(frontal lobe)
Limbic system
(emotional input)
Communication at
subconscious level
Hypothalamus
Overall integration
of ANS, the boss
Spinal cord
Urination, defecation,
erection, and ejaculation
reflexes
Brain stem
(reticular formation, etc.)
Regulation of pupil size,
respiration, heart, blood
pressure, swallowing, etc.

Hypothalamic Control
• Control may be direct or indirect (through the
reticular system)
• Centers of the hypothalamus control
• Heart activity and blood pressure
• Body temperature, water balance, and endocrine
activity
• Emotional stages (rage, pleasure) and biological
drives (hunger, thirst, sex)
• Reactions to fear and the “fight-or-flight” system

Developmental Aspects of the ANS
• During youth, ANS impairments are usually
due to injury
• In old age, ANS efficiency declines, partially
due to structural changes at preganglionic
axon terminals

Developmental Aspects of the ANS
• Effects of age on ANS
• Constipation
• Dry eyes
• Frequent eye infections
• Orthostatic hypotension
• Low blood pressure occurs because aging
pressure receptors respond less to changes
in blood pressure with changes in body
position and because of slowed responses
by sympathetic vasoconstrictor centers

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