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Central nervous system

 The nervous system with the endocrine system
controls and coordinates various functions of the

 The body has to make adjustments according to the

changes in its internal and external environments.

 These adjustments are essential for the maintenance

of homeostasis, as well as for existence.
Peripheral Nervous System
 Handles the CNS’s input and output.
 Contains all the portions of the NS outside the brain
and spinal cord.
 Contains sensory nerves and motor nerves
 Divided into autonomic nervous system and
somatic nervous system.
Peripheral Nervous System

Sensory Nerves
Motor Nerves
(to the brain)
(from the brain)

Carry messages from receptors in the

skin, muscles, and other internal Carry orders from CNS to
and external sense organs to the spinal muscles, glands to contract
cord and then to the brain and produce chemical messengers
 The ANS is part of the peripheral nervous system and it
controls many organs and muscles within the body.
 In most situations, we are unaware of the workings of the
ANS because it functions in an involuntary, reflexive
 For example, we do not notice when blood vessels
change size or when our heart beats faster.
The ANS is most important in two situations:

1- In emergencies that cause stress and require us to

"fight" or take "flight" (run away).

2- In no emergencies that allow us to "rest" and

 It is usual to divide the nervous system into somatic,
autonomic and integrated systems.
 The somatic nervous system provides voluntary motor
control of skeletal muscle.
The autonomic nervous system provides an involuntary
control of internal environment and the viscera.
 The two systems are anatomically separated form each

other, but functionally they cannot perform their work

independently, and they work with each other in an
integrated manner
Peripheral Nervous System
 Somatic NS  Autonomic NS
 Consists of nerves  Permits the

connected to sensory Involuntary functions

receptors and skeletal of blood vessels,Glands
muscles and internal organs
e.g.:- Bladder, stomach
 Permits voluntary
action (writing your heart
Characteristic Somatic nervous Autonomic N. system
Effectors Voluntary muscle Cardiac muscle glands,
s. muscle
General functions Adjustment to external Adjustment within
environment internal environment
Numbers of neurons 1 2

Ganglia outside the ------------ Chain ganglia,

CNS collateral ganglia or
terminal ganglia
Neurotransmitter acetylcholine Acetylcholine,
Center Anterior Horn cells Lateral Horn cells
Comparison of Autonomic and Somatic
Motor Systems
 Autonomic nervous system
 Chain of two motor neurons

 Preganglionic neuron

 Postganglionic neuron

 Conduction is slower due to thinly or unmyelinated axons


Pre-ganglionic Post-ganglionic
Sympathetic N.S. Parasympathetic N.S.

Like the accelerator of your Like the brakes in your car

car Slows the body down to keep
its rhythm

Mobilized the body for action Enables the body to conserve

and store energy
Preganglionic: short, synapse Preganglionic: long, synapse
within the lateral & collateral within the terminal ganglia

Postganglionic: long Postganglionic: short

Has a wide distributions Has a restricted distributions

• Often work in
opposition Autonomic Nervous System
• Cooperate to fine-
tune homeostasis
• Regulated by the
brain; hypothalamus,
pons and medulla
• Can also be regulated
by spinal reflexes; no
higher order input
• Pathways both consist
of a two neuron

Preganglionic neuron autonomic ganglion postganglionic neuron target

from CNS outside CNS
Fig. 45.34(TE Art)
Hypothalamus activates
sympathetic division of
nervous system
Heart rate, blood pressure,
and respiration increase
Adrenal medulla
epinephrine and

Blood flow to Stomach

skeletal muscles contractions
increases are inhibited
Sympathetic Parasympathetic
Fight or Flight, Dealing with Rest and Digest, Vegging
stress, thoracolumber, Craniosacral S2-S4,
intermediolateral column,
T1 -L2
Sympathetic nerve endings also activate the release of NE and E from the adrenal
Enhances effects of NE from sympathetic nerve endings
Adds the effects of E to the overall arousal (“fight or flight”) pattern
The Autonomic System
• Sometimes called the
“thoracolumbar” division
• Short preganglionic
neurons; long
postganglionic neurons;
ganglia are called the
chain ganglia
• Preganglionic neurons
secrete Ach onto nicotinic
• Postganglionic neurons
secrete NE on to  or 
• Target tissues are smooth
muscle, cardiac muscle,
endocrine glands, brown
• Sometimes called the
“cranio-sacral division
• Long preganglionic
• short postganglionic
neurons (often in the
target organ)
• Preganglionic neurons
secrete Ach on to
nicotinic receptors
• Postganglionic neurons
secrete Ach on to
muscarinic receptors
• Target tissues are smooth
muscle, cardiac muscle,
exocrine glands, brown
Anatomical Differences in Sympathetic
and Parasympathetic Divisions
Anatomical Differences in Sympathetic
and Parasympathetic Divisions
Similarities between Sympathetic & Parasympathetic
• Both are efferent (motor) systems: “visceromotor”
• Both involve regulation of the “internal” environment
generally outside of our conscious control:
• Both involve 2 neurons that synapse in a peripheral
ganglion and Innervate glands, smooth muscle,
cardiac muscle
CNS ganglion


preganglionic postganglionic
neuron neuron
Differences between Sympathetic & Parasympathetic

Location of Preganglionic Cell Bodies

Sympathetic Parasympathetic

Thoracolumbar Craniosacral
T1 – L2/L3 levels Brain: CN III, VII, IX, X
of the spinal cord Spinal cord: S2 – S4
Differences between Sympathetic & Parasympathetic

Relative Lengths of Neurons

ganglion target

short preganglionic long postganglionic

neuron neuron

ganglion target

long preganglionic short postganglionic

neuron neuron
Overview of the Autonomic Nervous System
Differences between Sympathetic & Parasympathetic
Sympathetic NE (ACh at sweat glands),
ACh, + + / -, α & ß receptors

• All preganglionics release acetylcholine (ACh) & are excitatory (+)

• Symp. postgangl. — norepinephrine (NE) & are excitatory (+) or inhibitory (-)
• Excitation or inhibition is a receptor-dependent & receptor-mediated response
Parasympathetic ACh, +

ACh, + / -
muscarinic receptors

• Parasymp. postgangl. — ACh & are excitatory (+) or inhibitory (-)

Overview of the Autonomic Nervous System
Differences between Sympathetic & Parasympathetic
Target Tissues
Sympathetic Parasympathetic
• Organs of head, neck, • Organs of head, neck,
trunk, & external genitalia trunk, & external genitalia
• Adrenal medulla
• Sweat glands in skin
• Arrector muscles of hair
• ALL vascular smooth muscle

» Sympathetic system is distributed to essentially all

tissues (because of vascular smooth muscle)
» Parasympathetic system never reaches limbs or
body wall (except for external genitalia)
Overview of ANS
Functional Differences

• “Fight or flight”
• Catabolic (expend energy)

• “Feed & breed”, “rest &
• Homeostasis

» Dual innervation of many

organs — having a brake
and an accelerator provides
more control
The reflex arc

The autonomic reflex The somatic reflex

arc arc
Origin Lateral horn cells Anterior horn cells

Efferent Relay in autonomic Supply the effector

ganglia outside the organ directly.
Inter ------------------------ present

Effector Smooth , cardiac skeletal

organs muscles
Visceral Reflex Arc
Autonomic and Somatic Motor
Structure of spinal nerves: Somatic pathways
dorsal root dorsal
dorsal root ganglion ramus
dorsal nerve somatic
ventral ventral somatic
horn ramus motor
gray ramus (GSE)
ventral root communicans white ramus
Mixed Spinal
Nerve ganglion
Structure of spinal nerves: Sympathetic pathways
gray column spinal


gray ramus
communicans white ramus
Sympathetic Division of the ANS
Sympathetic System: Postganglionic Cell Bodies
1. Paravertebral ganglia
• Located along sides of vertebrae
• United by preganglionics into Sympathetic Trunk
• Preganglionic neurons are thoracolumbar (T1–L2/L3) Paravertebral
but postganglionic neurons are cervical to coccyx ganglia
• Some preganglionics ascend or descend in trunk

trunk (chain)
synapse at
same level
• celiac ganglion
• sup. mesent. g.
• inf. mesent. g.

ascend to descend to
synapse at synapse at aorta
higher level lower level
Sympathetic System: Postganglionic Cell Bodies

2. Prevertebral (preaortic) ganglia

• Located anterior to abdominal aorta, in plexuses Paravertebral
surrounding its major branches ganglia
• Preganglionics reach prevertebral ganglia via
abdominopelvic splanchnic nerves
trunk (chain)

• celiac ganglion
• sup. mesent. g.
abdominopelvic • inf. mesent. g.
Sympathetic Trunk Ganglia
Sympathetic System: Summary
visceral tissues
1- Cervical division

4- somatic
tissues 2- Cardiopulmonary
(body wall, limbs) Splanchnics: postganglionic
fibers to thoracic viscera
via 31 spinal
to somatic tissues
of neck, body wall, 3- Abdominopelvic
and limbs Splanchnics: preganglionic
fibers to prevertebral ganglia,
sympathetic L2
postganglionic fibers to
trunk abdominopelvic viscera

1- Cervical division
Origin: T1-2
Course: preganglionic fibres reach the sympathetic
chain and then ascend upwards to relay
in the superior cervical ganglion.
Postganglionic neuron: pass from ganglion
to the following organs:-
 EYE: pupil dilatation, widening of palpebral fissure, exophthalmos,
Vasoconstriction of eye b.v. and Relaxation of ciliary muscle.
 Salivary gland : trophic secretion, Vasoconstriction of its blood
vessels and Squeezing of salivary secretion.
 Lacrimal gland: Trophic secretion and Vasoconstriction.

 Face skin blood vessel: Vasoconstriction of (Pale color).

 Sweet secretion: copious secretion.
 Hair: erection due to contraction of erector pilae muscles..
 Cerebral vessels: Week vasoconstriction
Sympathetic Pathways to the Head
(2) Cardiopulmonary division

Origin: Lateral horn cells of upper 4-5 thoracic segments.

Course: Preganglionic neurons reach the sympathetic chain
to relay in the three cervical ganglion and upper four
thoracic ganglion.
The postganglionic arise from these ganglia supply the
following structures:-
 Heart: Increase all properties of cardiac muscle
(contraction, rhythmicity, excitability, conductivity.
 Coronary vessels, its sympathetic supply. At first it
causes vasoconstriction, and then it causes vasodilatation
due to accumulation of metabolites.
 Bronchi: Broncho dilation, decrease bronchial secretions
and vasoconstriction of pulmonary blood vessels.
Sympathetic Pathways to Thoracic Organs
3- Splanchnic division

Origin: lateral horn cells of the lower six thoracic and upper four lumber segments.
Course: Preganglionic neurons originate from these segments reach the sympathetic
chain where they pass without relay, and then they divided into two branches:
(1) Greater splanchnic nerve
(2) Lesser splanchnic nerve.
Greater splanchnic nerve:
 Origin: Preganglionic nerves fibers emerge from lateral horn cells of lower six
thoracic segments and then relay in the collateral ganglion in the abdomen.
 Course: Postganglionic nerve fibers arise from these ganglia (celiac, superior
mesenteric and inferior mesenteric ganglia) and supply the abdominal organs
causing the following effects:
 Vasoconstriction: of most arteries of stomach, small intestine, proximal part of large
intestine, kidney, pancreas and liver.
 Relaxation of the musculature of: stomach, small intestine and proximal part of
large intestine.
 Contraction of sphincters: of the stomach and intestine leading to (food retention).
 Contraction of the capsule: of the spleen leading to evacuation of about 200 ml of
 Breakdown of the glucose in the liver: (glycogenolysis) leading to increase of
blood glucose level.
 Stimulation of adrenal medulla: Secrete adrenaline and noradrenalin.
Sympathetic Pathways to the Abdominal
Lesser splanchnic nerve
Origin: Preganglionic nerve fibers originate from the lateral horn cells
of the 12 thoracic and upper two lumber segments.
Course: 2 nerves from both sides unite together forming the presacral
nerve, which proceeds to pelvis and divided into two branches
(hypogastric nerves), then relay in the inferior mesenteric ganglion.
Postganglionic nerve fiber supplies the following pelvic viscera:
Urinary bladder: Relaxation of its wall.
 Contraction of internal urethral sphincter.

 Leading to urine retention.

 Relaxation of the distal part of large intestine.

 Relaxation of the rectum wall.

 Contraction of the internal anal sphincter.

 Leading to feces retention.

Genital organs:
- Vasoconstriction of its blood vessels.
 Leading to shrinkage of penis and clitoris.

Vas deference:
- Contraction of its wall, and wall of
seminal vesicles, ejaculatory ducts and
- Leading to ejaculation.
Sympathetic Pathways to the Pelvic Organs
(4) Somatic division
Origin: Preganglionic nerve fibers arise from all lateral horn
cells of all sympathetic segments, and then relay in the
cervical and sympathetic chain ganglia.
Course: Postganglionic nerve fibers emerge from these
ganglia proceeds outside the central nervous system to
return back to spinal cord to join the spinal nerve when it
comes out from the anterior horn cells, and supply the
following structures:
 Vasoconstriction giving the pale color of the skin.
 Stimulation of the sweet glands, the eccrine glands give copious secretion,
while the apocrine glands give thick odoriferous secretion.
 Hair erection.
Skeletal muscle:
 Its blood vessels show vasodilatation (V.D.) due to cholinergic effect or
vasoconstriction (V.C.) due to a adrenergic effect.
 The type of stimulation depends upon the nature of stimulation.
 Muscles: its stimulation causing delayed fatigue and early recovery.
The Role of the Adrenal Medulla
in the Sympathetic Division
 Major organ of the sympathetic nervous
 Secretes great quantities epinephrine (a little
 Stimulated to secrete by preganglionic
sympathetic fibers
The Adrenal Medulla
Cranial outflow
• Four ganglia in head
• Vagus nerve (CN X) is major
preganglionic parasymp.
supply to thorax & abdomen
• Synapse in ganglia within
wall of the target organs (e.g.,
enteric plexus of GI tract)

Sacral outflow
• S2–S4 via pelvic splanchnics
• Hindgut, pelvic viscera, and
external genitalia
Clinical Relevance
» Surgery for colorectal cancer
puts pelvic splanchnics at risk
» Damage causes bladder &
sexual dysfunction
The Parasympathetic Division
 Cranial outflow
 Comes from the brain
 Innervates organs of the head, neck, thorax, and
 Sacral outflow
 Supplies remaining abdominal and pelvic organs
Cranial Nerves
 Attach to the brain and pass through foramina
of the skull
 Numbered from I–XII
 Cranial nerves I and II attach to the forebrain
 All others attach to the brain stem
 Primarily serve head and neck structures
 The vagus nerve (X) extends into the abdomen
CN I: Olfactory Nerves
 Sensory nerves of smell
CN II: Optic Nerve
 Sensory nerve of vision
CN III: Oculomotor Nerve
 Innervates four of the extrinsic eye muscles
CN IV: Trochlear Nerve
 Innervates an extrinsic eye muscle
CN V: Trigeminal Nerve
 Provides sensory innervation to the face
 Motor innervation to chewing muscles
CN VI: Abducens Nerve
 Abducts the eyeball
CN VII: Facial Nerve
 Innervates muscles of facial expression
 Sensory innervation of face
 Taste
CN VIII: Vestibulocochlear
 Sensory nerve of hearing and balance
CN IX: Glossopharyngeal Nerve
 Sensory and motor innervation of structures of the tongue
and pharynx
 Taste
CN X: Vagus Nerve
 A mixed sensory and motor nerve
 Main parasympathetic nerve
 “Wanders” into thorax and abdomen
CN XI: Accessory Nerve
 An accessory part of the vagus nerve
 Somatic motor function of pharynx, larynx, neck
CN XII: Hypoglossal Nerve
 Runs inferior to the tongue
 Innervates the tongue muscles
Cranial Outflow
 Preganglionic fibers run via:
 Oculomotor nerve (III)
 Facial nerve (VII)
 Glossopharyngeal nerve (IX)
 Vagus nerve (X)
 Cell bodies located in cranial nerve nuclei in
the brain stem
CN III: Oculomotor Nerve
Origin: Edinger-Westphal nucleus
at midbrain.
preganglionic from E-W nucleus
to rely in the ciliary ganglion.
Postganglionic supply:
1- pupillconstrictor muscle
2- ciliary muscle.
3- four of the extrinsic eye
Its stimulation leads to miosis,
accommodation to neat vision
and movements of the eye ball.
CN III: Oculomotor Nerve
 Innervates four of the extrinsic eye muscles
CN VII: Facial Nerve
Origin: The superior salivary nucleus which is a part of facial
nucleus in the lower part of pons.
Course: Preganglionic nerve fibers run in the chorda tympani
nerve which is a part of facial nerve and relay in:-
- Submaxillary ganglion
- Sphenopalatine ganglion.
 Postganglionic nerve arises from Submaxillary ganglion

supply submandibular and sublingual salivary glands and

anterior 2/3 of the tongue.
 Postganglionic nerve arises from Sphenopalatine ganglion

supply the mucosa of the soft palate and nasopharynx and

Lacrimal glands.
 Its stimulation causes vasodilatation and secretion at their

effector organs.
CN VII: Facial Nerve
 Innervates muscles of facial expression
 Sensory innervation of face
 Taste
CN IX: Glossopharyngeal Nerve
Origin: Glossopharyngeal nerve nucleus in the
upper part of the medulla oblongata called
inferior salivary nucleus, and then relay in the
otic ganglion.
Course: Postganglionic nerve fibers arise from
otic ganglion supply the parotid salivary gland
and posterior 1/3 of the tongue
Its stimulation causes vasodilatation and
secretion at their effector organs
CN IX: Glossopharyngeal Nerve
 Sensory and motor innervation of structures of the tongue
and pharynx
 Taste
CN X: Vagus Nerve
Origin: Dorsal vagus nucleus in medulla oblongata
Course: Postganglionic nerve fibers from the terminal ganglia
which supplied from dorsal vagus nucleus and supply the
following structures:
 HEART: The vagus nerve supplies the both auricles and

don't supply the ventricles (and this called vagus escape

 Its stimulation produces inhibition of all cardiac properties
(decrease heart rate, decrease contractility and decrease
 Its stimulation causes vasoconstriction of coronary vessels and
reduction of O2 consumption by cardiac muscle.
 These responses lead to bradycardia.
 Lungs: Vagus stimulation causes:
 Bronchoconstriction.
 Increased bronchial secretion.
 Vasodilatation of pulmonary blood vessels.
 These responses lead to precipitation of asthma.
Gastrointestinal tract: Vagus stimulation causes:
 Contraction of walls of esophagus, stomach, small intestine and
proximal part of large intestine.
 Relaxation of their corresponding sphincter.
 These responses promote deglutition, increased secretion of
GIT and evacuation of foods.
 Gall bladder: Vagus stimulation causes:
 Contraction of the gall bladder wall.
 Relaxation of its sphincter.
 These responses lead to evacuation of the gall bladder.
CN X: Vagus Nerve
Sacral Outflow
Origin: Preganglionic nerve fibers arise from the lateral
horn cells of the 2nd, 3rd and 4th sacral segments.
Course: These preganglionic passes without relay, then the
right and left branches unit together to form the pelvic
nerve, the pelvic nerve relay in the terminal ganglia,
where the postganglionic nerve fibers emerge and supply
the following structures:-
Urinary bladder: parasympathetic stimulation causes:
- Contraction of the bladder wall
- Relaxation of its sphincter.
- These responses lead to micturition.
Rectum and descending colon:
parasympathetic stimulation causes:
- Contraction of its wall.
- Relaxation of internal anal sphincter.
- These responses lead to defecation.
Seminal vesicles and prostate:
parasympathetic stimulation -causes:
- Secretion of these glands.
Erectile tissue: parasympathetic stimulation causes:
- Vasodilatation which lead to erection.
Chemical transmission
The traveling of signal in the nervous system
between different neurons is mediated by the
effect of a chemical substance released at the
nerve terminal called chemical transmitter.
In the sympathetic nervous system the chemical
transmitter is adrenaline, noradrenaline or
sometimes acetylcholine.
When the chemical transmitter is adrenaline the
nerve fiber is called adrenergic, but when the
chemical transmitter is acetylcholine, the nerve
fiber is called cholinergic.
Nerves Contact Other Cells at Synapses
 The synapse is the relay point where information is
conveyed from neuron to neuron by chemical transmitters.
 At a synapse the axon usually enlarges to from a button '

which is the information delivering part of the junction.

 The terminal button contains tiny spherical structures called
synaptic vesicles, each of which can hold several thousand
molecules of chemical transmitter.
 On the arrival of a nerve impulse at the terminal button,

some the vesicles discharge their contents into the narrow

cleft that separates the membrane of another cell's dendrite,
which is designated to receive the chemical message.
 Chemical transmitters carry the signal across
 Chemical transmitters are made and stored in

the presynaptic terminal

 The transmitter diffuses across the synaptic

gap and binds to a receptor in the postsynaptic

 Binding of the Transmitter Produces an

excitatory postsynaptic potential EPSP or

inhibitory postsynaptic potential IPSP
The Transmitter is Broken down and
 Once the signal has been delivered the

transmitter must be removed so that new

signals may be received
 In some cases the transmitter is broken down

by an enzyme in the synapse

 In other cases the transmitter is recycled- it is

transported back into the presynaptic nerve

 In still other cases these 2 methods are

 Important neurotransmitter in central and
peripheral nervous systems.
 Acetylcholine is synthesized in the nerve
1- Acetyl-coenzyme A (AcCoA) is
manufacured in mitochondria.
2- Choline is accumulated in the teminals by
active uptake from interstitial fluid.
3- AcCoA + choline = acetylcholine.
Acetylcholine storage
 Acetylcholine is stored in vesciles in the verve terminal after
its synthesis, each vesicle contains approximatly 104 Ach
molecules, which are released as a single packet.

Acetylcholine release
The arrival of the action potential to the nerve terminal, it leads
to increase in the permeability of the terminal to Ca++ influx.
 Ca++ recat with synapsin that bind the vesciles, which on its

unbinding the vesciles sweeps to attach to the presynaptic

 The vesciles rupture and the acetylcholine released to the

synaptic cleft.
 Acetylcholine act on its specific receptors on the postsynaptic
Acetylcholine release sites
1-Preganglionic nerve fibres of both
sympathetic and parasympathetic divisions
of the autonomic nervous system.
2-Postganglionic nerves of the
parasympathetic division.
3- The sympathetic innervation of sweet
4- Neuromuscular junction.
5- Autonomic ganglion to the adrenal gland.
Neurotransmitter release sites
Acetylcholine inactivation
In synaptic cleft, Acetylcholinesterase
breaks it down into acetate and choline.
50% of choline then re up taken into
presynaptic neuron.
Acetylcholine receptors
Acetylcholine effects on the tissue are the result of its action
on the receptor present in the membrane of the effector
Several types of Ach receptors have been characterized by
their sensetivity to agonists (which mimic the action of
Ach) or antagonists (which specifically block the action
of Ach).
 Two types of cholinergic receptors are well known:

 Nicotinic receptors which are easily activated by agonist

molocule such as nicotine and

 Muscarinic receptors: which are sensitive to muscarine.
Cholinergic receptors
Nicotinic receptors Muscarinic receptors
(Central) (peripheral )
Types Two types:- M1, M2 (cardiac), M3
Ganglionic (glandular&smooth
Neruomuscular muscle) M4
(brain).M5,M6 and M7.
Stimulated Nicotine in small doses, Muscarine, Ach,
by Ach, metacholine carbarcholine

Blocked by Nicoitin in large doses- Atropine

decameyhonium scopolamine
site Autonomic ganglia Parasympathetic
M.E.P (pre-postganglionic)
Adrenal medulla Sympathetic
Preganglionic neuron. postganglionic nerve
endings (sweat glands &
skeletal muscle).
Nicotinic Receptors
 Located in the ganglia of both the
 Named “nicotinic” because can be stimulated
by the alkaloid nicotine
Muscarinic Receptors
 Located postsynaptically:
 Smooth muscle
 Cardiac muscle
 Glands of parasympathetic fibers
 Effector organs of cholinergic sympathetic fibers

 Named “muscarinic” because can be

stimulated by the alkaloid muscarine
Parasympathetic (Cholinergic) Drugs
Subdivisions of the Autonomic Nervous System

Sympathetic Parasympathetic

Primary norepinephrine
Neurotransmitter epinephrine (~20%)

Receptors Adrenergic GPCRs Muscarinic GPCRs

&  1 – IP3/DAG, [Ca2+]i PKC M1 – IP3/DAG, [Ca2+]i PKC
Second  2 - cAMP/PKA M2 – cAMP/PKA, PI(3)K
Messenger M3 – cAMP/PKA,
Systems  1 - cAMP/PKA IP3/DAG, [Ca2+]i PKC
 2 - cAMP/PKA M4 –
 3 - cAMP/PKA M5 – IP3/DAG, [Ca2+]i PKC

Adrenal Medulla
Comparison of sympathetic and
Parasympathetic Pathways

 Neurotransmitters
 Receptors
Drugs Affecting the
Autonomic Nervous System
Parasympathomimetic drugs:
These are drugs which exert an action similar to
acetylcholine and there are two types:-
- Drugs directly stimulate cholinergic receptors -
Drugs inhibit cholinesterase enzyme.
Parasympatholytic Drugs:
These drugs antagonize the action of acetylcholine.
Cholinergic Agents
 Drugs that stimulate the parasympathetic
nervous system (PSNS).
 Drugs that mimic the effects of the PSNS
 Acetylcholine (ACh)
Parasympathomimetic drugs
These are drugs which exert an action similar to the action of
acetylcholine and it is divided into two groups:
(A) Drugs that directly stimulate the cholinergic receptors: These
include Ach derivatives that not hydrolyzed rapidly by cholinesterase
e.g. metacholine, carbachol, poiolocarpine and muscarine.
(B) Drugs that inhibit the cholinesterase enzyme: These drugs
preserve the action of Ach by preventing the action of cholinesterase
enzyme and they are two types:-
(1) Drugs which has a reversible effect i.e. their action is temporary e.g.
eserine (phyostigmine) and prostigmine (neostigmine) .
 - Eserine: is a generalized drugs which causes generalized blocking allover the
body, thus we use it locally as an eye drops in treatment of glaucoma otherwise it
will cause generalized parasympathetic effect.
 - Neostigmine:It was used in treatment of myasthenia gravis due to its direct action
on the motor end plate.
(2) Drugs which have irreversible effect i.e. their action are
prolonged e.g. parathion (an insecticide) and D.F.P.
(Diisopropyflurophosphate), which is a toxic nerve gas.
Parasympatholytic Drugs
 These drugs which antagonize the action of
Ach by one of the following mechanisms:-
 Competitive inhibition : These drugs occupy

the Ach receptors and present its action .

 Persistent depolarization : These drugs cause

prolonged depolarization of Ach receptor thus

they prevent the excitation of the receptor by
the released Ach.
Parasympatholytic drugs
Muscarinic like action Ganglion blockers Neuromuscular blocker
These drugs block the These drugs block the action These drugs block the
action of Ach at cholinergic of Ach at nicotinic recpotors nicotinic like action of Ach at
receptors by blocking the neuromuscular junction.
action of Ach at muscarinic

e.g.-AtropineHomatropine e.g. e.g.

Hyoscine -Nicotine in large doses. - curare
- Arfonad
- Hexamethonium

Mechanism of action- Competitive inhibition. Competitive inhibition.

competitive inhibition -Persistent depolarization

Clinical use: - Ganglion blocker used for - Curare is used as a muscle

Atropine used for:-- blocking conduction in relaxant
dilation of pupil- relive sympathetic ganglion of
spasm- prevent bronchial hypertension.
Sympathetic (Adrenergic) Drugs
from phe, diet, or protein
breakdown DHBR

Tyrosine L-Dopa
Tyrosine hydroxylase 2 Dopa
(rate-determining step) H O decarboxylase
O2 2
H2O 3 O2 CO
DPN OHase in neuro-
scretory granules ascorbate
Norepinephrine Dopamine
Dopamine hydroxylase
Parkinson’s disease: local
Epinephrine deficiency of dopamine
SAM from
synthesis; L-dopa boosts
metabolism of 4 PNMT specific to production
Met adrenal medulla

Biosynthesis of catecholamines. BH2/BH4, dihydro/tetrahydrobiopterin; DHBR,

dihydrobiopterin reductase; PNMT, phenylethanolamine N-CH3 transferase; SAH, S-
adenosylhomocysteine; SAM, S-adenosylmethionine
Regulation of the release of Stress
catecholamines and synthesis of Chronic
epinephrine in the adrenal regulation
medulla chromaffin cell. ACTH
from adrenal
Cortisol cortex via intra-
Tyrosine adrenal portal
Acute L-Dopa DPN
.. .. Ca2+ 

 E E E
acetylcholine promotes NE E
Adrenal Medulla exocytosis
Chromaffin Cell E E
Epinephrine COMT + MAO
Vanillylmandelic acid

Dopamine Homovanillic acid

Neuronal re-uptake and degradation of catecholamines quickly

terminates hormonal or neurotransmitter activity.
Cocaine binds to dopamine receptor to block re-uptake of dopamine
Dopamine continues to stimulate receptors of the postsynaptic nerve.

Degradation of epinephrine, norepinephrine and dopamine via

monoamine oxidase (MAO) and catechol‑O‑methyl-
transferase (COMT)
Table 1. Classification of Adrenergic Hormone Receptors

Receptor Agonists G protein
alpha1 (1) E>NE IP3/Ca2+; DAG Gq
alpha2 (2) NE>E  cyclic AMP Gi
beta1 (1) E=NE  cyclic AMP Gs
beta2 (2) E>>NE  cyclic AMP Gs
E = epinephrine; NE = norepinephrine
Synthetic agonists:
isoproterenol binds to beta receptors
phenylephrine binds to alpha receptors (nose spray action)

Synthetic antagonists:
propranolol binds to beta receptors
phentolamine binds to alpha receptors


Figure 4. Model for the structure of the  2-adrenergic receptor

Table 2. Metabolic and muscle contraction responses to catecholamine binding to
various adrenergic receptors. Responses in italics indicate decreases of the indicated
process (i.e., decreased flux through a pathway or muscle relaxation)

 1-receptor  2-receptor  1-receptor  2-receptor

(IP3, DAG) ( cAMP) ( cAMP) ( cAMP)
Carbohydrate  liver glycogenolysis;
No effect No effect
metabolism glycogenolysis  liver gluconeogenesis;
 glycogenesis
No effect  lipolysis  lipolysis No effect
Hormone  insulin  insulin and glucagon
No effect No effect
secretion secretion secretion
Smooth muscle - muscle - Myocardial Smooth muscle relaxation -
Muscle blood vessels, some
- rate, bronchi, blood vessels,
contraction genitourinary vascular;
force GI tract, genitourinary tract
tract GI tract
1 or 2 2 receptor

Gs Gi
s  i 
  
  
 
ACTIVE X inactive
adenylyl adenylyl
cyclase adenylyl
ATP cyclic AMP
Figure 5. Mechanisms of 1, 2, and 2 agonist effects on adenylyl cyclase activity

epinephrine/ norepinephrine major elements in the "fight or flight" response

acute, integrated adjustment of many complex processes in organs vital to the
response (e.g., brain, muscles, cardiopulmonary system, liver)
occurs at the expense of other organs less immediately involved (e.g., skin, GI).
rapidly mobilizes fatty acids as the primary fuel for muscle action
increases muscle glycogenolysis
mobilizes glucose for the brain by  hepatic glycogenolysis/
preserves glucose for CNS by  insulin release leading to reduced glucose
uptake by muscle/ adipose
increases cardiac output
norepinephrine elicits responses of the CV system -  blood flow and  insulin
Figure 6. Mechanisms for terminating the signal generated by epinephrine
binding to a -adrenergic receptor
epinephrine [1]

[2]  GTP 
[5] [3] [4]
[6] OH OH
ATP cAMP AMP phosphorylation
phosphodiesterase of -receptor by binding of -arrestin
-ARK decreases further inactivates
activity even with receptor despite
activated PKA bound hormone bound hormone
insulin activation of protein
phosphatase to dephosphorylate
OH [7] OP enzymes
1 found on heart muscle and in certain cells of the kidney
B2 found in certain blood vessels, smooth muscle of airways; found where sympathetic
neurons ARE NOT
1 receptors are found most commonly in sympathetic target tissues
A2 receptors are found in the GI tract and pancreas (relaxation)