ABOUT NERVOUS SYSTEM

1. Nervous System
(General outline of central
nervous system and autonomic
nervous system)
Supriya Mana

2. Composition of Nervous System
• Two main divisions
– 1) Central Nervous
system (CNS) brain and
spinal chord
– 2)Peripheral Nervous
System (PNS) nerves

3. Remember from Homeostasis
• Message is received from sensory receptor
along sensory neuron (afferent pathway)
• Messages reaches brain and is integrated
(control center)
• Reaction command sent down efferent
pathway along motor neuron (motor
output)

4. Types of Motor Actions
• Somatic
– Happens in skeletal
muscle
– voluntary
• Autonomic
– Happens in smooth and
cardiac muscle
– Involuntary
– 2 parts
• Sympathetic and
parasympathetic

5. Cells of the Nervous System
• Broken down into two
groups
– 1) supporting cells
– 2) neurons

6. Examples of Neuroglia (supporting cells)
• Astrocytes – anchor
neurons to capillaries
• Microglia – phagocytes
(digest debris and dead
cells)
• Ependymal cells- ciliated;
always on surface near
spinal fluid; circulates
fluid

7. One more Neuroglial cell (in CNS)
• Oligodendrocytes –
fatty; insulated nerve
fibers
• Produce myelin sheath
which surround and
insulate the nerve fiber

8. In PNS
• Instead of
oligodendrocytes, they
have Schwann cells,
which insulate the
nerve fiber
• Satellite cells – form
protective layer around
nerve cell body

9. Neurons
• Specifically designed to
transmit message
(nerve impulse)

10. Parts of a Neuron
• 1)Cell Body- contains
nucleus
• 2) fiber (process)-
carries message to next
neuron
– Toward cell body =
dendrites
– Away from cell body =
axon

11. Axonal Terminal
• As an axon ends, it
branches into
hundreds of
synapses.
• Releases
neurotransmitters to
next neuron or
muscle

12. Myelination of Neurons
• In CNS, the fatty
covering is
oligodendrocyte
• In PNS, fatty myelin
forms Schwann cells,
which increase
transmission rate.
• Gaps between
Schwann cells= Nodes
of Ranvier

13. INTRODUCTION
• Much of the action of the body in maintaining
such as cardiovascular, gastrointestinal and
thermal homeostasis occurs through the
autonomic nervous system (ANS).
• The ANS is our primary defense against
challenges, to maintain homeostasis. It
provides involuntary control and organization
of both maintenance and stress responses.
13

14. FUNCTIONAL ANATOMY
Nervous System
Central Nervous
System
Peripheral
Nervous System
Somatic Autonomic
Sympathetic Parasympathetic
Enteric
Nervous
System
14

15. DIFFeReNCe
beTweeNSomatic Autonomic
Organ supplied Skeletal muscles All other organs
Distal most synapse Within CNS Outside the CNS(i.e. ganglia)
Nerve fibers Myelinated Preganglionic - myelinated
Postganglionic- non­myelinated
Peripheral plexus
formation
Absent Present
Efferent transmitter ACH ACH, Nor-adrenaline
Effect of nerve section
on organ supplied
Paralysis and Atrophy Activity maintained, no
Atrophy 15

16. AUTONOMIC NERVOUS SYSTEM

17. 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
Ganglion
Post-ganglionic

18. Autonomic Nervous System
• Often work in
opposition
• 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 system
Preganglionic neuron autonomic ganglion postganglionic neuron target
from CNS outside CNS

19. Fig. 45.34(TE Art)Hypothalamus activates
sympathetic division of
nervous system
Heart rate, blood pressure,
and respiration increase
Blood flow to
skeletal muscles
increases
Stomach
contractions
are inhibited
Adrenal medulla
secretes
epinephrine and
norepinephrine

21. Sympathetic
Fight or Flight, Dealing with stress,
thoracolumber,
intermediolateral column, T1 -L2
Parasympathetic
Rest and Digest, Vegging
Craniosacral S2-S4,

22. Sympathetic nerve endings also activate the release of NE and E from the adrenal
medulla
Enhances effects of NE from sympathetic nerve endings

23. The Autonomic SystemThe Autonomic System

24. Sympathetic
• Sometimes called the
“thoracolumbar” division
• Short preganglionic neurons;
long postganglionic neurons;
ganglia are called the chain
ganglia
• Preganglionic neurons secrete
Ach onto nicotinic receptors
• Postganglionic neurons
secrete NE on to α or β
receptors
• Target tissues are smooth
muscle, cardiac muscle,
endocrine glands, brown fat

25. Parasympathetic
•Sometimes called the
“cranio-sacral division
•Long preganglionic
neurons;
•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
fat

26. Anatomical Differences in Sympathetic
and Parasympathetic Divisions

27. Anatomical Differences in Sympathetic
and Parasympathetic Divisions

28. Similarities between Sympathetic & ParasympatheticSimilarities between Sympathetic & Parasympathetic
• Both are efferent (motor) systems: “visceromotor”
• Both involve regulation of the “internal” environment
generally outside of our conscious control:
“autonomous”
• Both involve 2 neurons that synapse in a peripheral
ganglion and Innervate glands, smooth muscle,
cardiac muscle
CNS ganglion
preganglionic
neuron
postganglionic
neuron
glands
smooth
muscle
cardiac
muscle

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

30. Sympathetic
CNS ganglion
short preganglionic
neuron
long postganglionic
neuron
target
Parasympathetic
CNS ganglion
long preganglionic
neuron
target
short postganglionic
neuron
Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic
Relative Lengths of Neurons

31. Parasympathetic
Overview of the Autonomic Nervous SystemOverview of the Autonomic Nervous System
Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic
Neurotransmitters
ACh, +
NE (ACh at sweat glands),
+ / -, α & ß receptors
ACh, + / -
muscarinic receptors
• All preganglionics release acetylcholine (ACh) & are excitatory (+)
• Symp. postgangl. — norepinephrine (NE) & are excitatory (+) or inhibitory (-)
• Parasymp. postgangl. — ACh & are excitatory (+) or inhibitory (-)
Sympathetic
• Excitation or inhibition is a receptor-dependent & receptor-mediated response
ACh, +

32. Overview of the Autonomic Nervous SystemOverview of the Autonomic Nervous System
Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic
Target Tissues
ParasympatheticSympathetic
• Organs of head, neck,
trunk, & external genitalia
• Organs of head, neck,
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)

33. Overview of ANSOverview of ANS
Functional Differences
Sympathetic
• “Fight or flight”
• Catabolic (expend energy)
Parasympathetic
• “Feed & breed”, “rest &
digest”
• Homeostasis
» Dual innervation of many
organs — having a brake
and an accelerator provides
more control

35. The reflex arc
The autonomic reflex
arc
The somatic reflex
arc
Origin Lateral horn cells Anterior horn cells
Efferent Relay in autonomic
ganglia outside the
CNS.
Supply the effector
organ directly.
Inter
neuron
------------------------ present
Effector
organs
Smooth , cardiac
muscles
skeletal

37. Visceral Reflex Arc

38. Fig. 45.32(TE Art)
Viscera
Autonomic
ganglion
Postganglionic neuron
Autonomic motor reflex
Interneuron Dorsal root
ganglion
Preganglionic
neuron
Sensory
neuron
Spinal
cord

39. Autonomic and Somatic Motor
Systems

40. Structure of spinal nerves: Somatic pathwaysStructure of spinal nerves: Somatic pathways
dorsal root
dorsal root
ganglion
ventral root
spinal
nerve
dorsal
ramus
ventral
ramus
dorsal
horn
ventral
horn
somaticsomatic
sensorysensory
nervenerve
(GSA)(GSA)
somaticsomatic
motormotor
nervenerve
(GSE)(GSE)
CNS
inter-
neuron
Mixed SpinalMixed Spinal
NerveNerve
Mixed SpinalMixed Spinal
NerveNerve
gray ramus
communicans white ramus
communicans
sympathetic
ganglion

41. spinal
nerve
dorsal
ramus
ventral
ramus
gray ramus
communicans white ramus
communicans
sympathetic
ganglion
intermediolateral
gray column
Structure of spinal nerves: Sympathetic pathwaysStructure of spinal nerves: Sympathetic pathways

42. Sympathetic Division of the ANS

43. somatic tissues
(body wall, limbs)
visceral tissues
(organs)
Sympathetic System: Preganglionic Cell BodiesSympathetic System: Preganglionic Cell Bodies
• Preganglionic cell bodies in
intermediolateral gray
• T1 — L2/L3
• Somatotopic organization
intermediolateral
gray columns
lateral
horn
T1 –
L2/L3
Clinical Relevance
» dysfunction due to cord injury
» spinal nerve impingement & OMM
» referred pain

44. Sympathetic System: Postganglionic Cell BodiesSympathetic System: Postganglionic Cell Bodies
Paravertebral
ganglia
Prevertebral
ganglia
• celiac ganglion
• sup. mesent. g.
• inf. mesent. g.
aorta
sympathetic
trunk (chain)
1. Paravertebral ganglia
• Located along sides of vertebrae
• United by preganglionics into Sympathetic Trunk
• Preganglionic neurons are thoracolumbar (T1–L2/L3)
but postganglionic neurons are cervical to coccyx
• Some preganglionics ascend or descend in trunk
synapse at
same level
ascend to
synapse at
higher level
descend to
synapse at
lower level

45. Sympathetic System: Postganglionic Cell BodiesSympathetic System: Postganglionic Cell Bodies
Paravertebral
ganglia
Prevertebral
ganglia
• celiac ganglion
• sup. mesent. g.
• inf. mesent. g.
aorta
sympathetic
trunk (chain)
2. Prevertebral (preaortic) ganglia
• Located anterior to abdominal aorta, in plexuses
surrounding its major branches
• Preganglionics reach prevertebral ganglia via
abdominopelvic splanchnic nerves
abdominopelvic
splanchnic
nerve

46. Sympathetic Trunk Ganglia

47. Sympathetic System: SummarySympathetic System: Summary
T1
L2
4- somatic
tissues
(body wall, limbs)
visceral tissues
(organs)
postganglionics
via 31 spinal
nerves
to somatic tissues
of neck, body wall,
and limbs
sympathetic
trunk
prevertebral
ganglia
2- Cardiopulmonary
Splanchnics: postganglionic
fibers to thoracic viscera
3- Abdominopelvic
Splanchnics: preganglionic
fibers to prevertebral ganglia,
postganglionic fibers to
abdominopelvic viscera
1- Cervical division

48. 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: Weak vasoconstriction

49. Sympathetic Pathways to the Head

50. (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.

51. Sympathetic Pathways to Thoracic Organs

52. 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 blood.
• Breakdown of the glucose in the liver: (glycogenolysis) leading to increase of blood glucose
level.
• Stimulation of adrenal medulla: Secrete adrenaline and noradrenalin.

53. Sympathetic Pathways to the Abdominal Organs

56. 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.
Rectum:
– Relaxation of the distal part of large intestine.
– Relaxation of the rectum wall.
– Contraction of the internal anal sphincter.
– Leading to feces retention.

57. Genital organs:
- Vasoconstriction of its blood vessels.
–Leading to shrinkage of penis and clitoris.
Vas deferens:
- Contraction of its wall, and wall of
seminal vesicles, ejaculatory ducts and
prostate
- Leading to ejaculation.

58. Sympathetic Pathways to the Pelvic Organs

59. (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:
Skin:
• 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.

60. 4- somatic tissues
(body wall, limbs)
postganglionics
via 31 spinal nerves
to somatic tissues of neck,
body wall, and limbs
sympathetic
trunk

61. Sympathetic Pathways to Periphery
Figure 15.9

62. The Role of the Adrenal Medulla in the
Sympathetic Division
• Major organ of the sympathetic nervous
system
• Secretes great quantities epinephrine (a little
norepinephrine)
• Stimulated to secrete by preganglionic
sympathetic fibers

63. The Adrenal Medulla

64. ParasympatheticParasympathetic
PathwaysPathways
Cranial outflow
• CN III, VII, IX, X
• 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

65. The Parasympathetic Division
• Cranial outflow
– Comes from the brain
– Innervates organs of the head, neck, thorax, and
abdomen
• Sacral outflow
– Supplies remaining abdominal and pelvic organs

66. The Parasympathetic Division

67. 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

68. The 12 Pairs of Cranial Nerves

69. CN I: Olfactory Nerves
• Sensory nerves of smell

70. CN II: Optic Nerve
• Sensory nerve of vision

71. CN III: Oculomotor Nerve
• Innervates four of the extrinsic eye muscles

72. CN IV: Trochlear Nerve
• Innervates an extrinsic eye muscle

73. CN V: Trigeminal Nerve
• Provides sensory innervation to the face
– Motor innervation to chewing muscles

74. CN VI: Abducens Nerve
• Abducts the eyeball

75. CN VII: Facial Nerve
• Innervates muscles of facial expression
• Sensory innervation of face
• Taste

76. CN VIII: Vestibulocochlear Nerve
• Sensory nerve of hearing and balance

77. CN IX: Glossopharyngeal Nerve
• Sensory and motor innervation of structures of
the tongue and pharynx
• Taste

78. CN X: Vagus Nerve
• A mixed sensory and motor nerve
• Main parasympathetic nerve
– “Wanders” into thorax and abdomen

79. CN XI: Accessory Nerve
• An accessory part of the vagus nerve
• Somatic motor function of pharynx, larynx, neck
muscles

80. CN XII: Hypoglossal Nerve
• Runs inferior to the tongue
– Innervates the tongue muscles

81. 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

82. CN III: Oculomotor Nerve
Origin: Edinger-Westphal nucleus at
midbrain.
Course:
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 muscles.
Its stimulation leads to miosis,
accommodation to neat vision and
movements of the eye ball.

83. CN III: Oculomotor Nerve
• Innervates four of the extrinsic eye muscles

84. 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.

85. CN VII: Facial Nerve
• Innervates muscles of facial expression
• Sensory innervation of face
• Taste

86. 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

87. CN IX: Glossopharyngeal Nerve
• Sensory and motor innervation of structures of
the tongue and pharynx
• Taste

88. 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
phenomena).
• Its stimulation produces inhibition of all cardiac properties
(decrease heart rate, decrease contractility and decrease
conductivity).
• Its stimulation causes vasoconstriction of coronary vessels and
reduction of O2 consumption by cardiac muscle.
• These responses lead to bradycardia.

89. • 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.

90. CN X: Vagus Nerve

91. 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.

92. 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.

93. 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.

94. 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.

95. • Chemical transmitters carry the signal across
synapses
• 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 membrane.
• Binding of the Transmitter Produces an
excitatory postsynaptic potential EPSP or
inhibitory postsynaptic potential IPSP

96. The Transmitter is Broken down and Recycled
• 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
combined

97. Acetylcholine
• Important neurotransmitter in central and
peripheral nervous systems.
• Acetylcholine is synthesized in the nerve
terminal.
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.

98. 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
membrane.
• The vesciles rupture and the acetylcholine released to the
synaptic cleft.
• Acetylcholine act on its specific receptors on the postsynaptic
membrane.

99. 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
glands.
4- Neuromuscular junction.
5- Autonomic ganglion to the adrenal gland.

100. Neurotransmitter release sites

101. Acetylcholine inactivation
In synaptic cleft, Acetylcholinesterase
breaks it down into acetate and choline.
50% of choline then re up taken into
presynaptic neuron.

102. Acetylcholine receptors
Acetylcholine effects on the tissue are the result of its
action on the receptor present in the membrane of the
effector cells.
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.

103. Cholinergic receptors
Nicotinic receptors
(Central)
Muscarinic receptors
(peripheral )
Types Two types:-
Ganglionic
Neruomuscular
M1, M2 (cardiac), M3
(glandular&smooth
muscle) M4
(brain).M5,M6 and M7.
Stimulated
by
Nicotine in small
doses, Ach,
metacholine
Muscarine, Ach,
carbarcholine
Blocked by Nicoitin in large doses-
decameyhonium
d-tubourarine-
Atropine
scopolamine
site Autonomic ganglia
M.E.P
Adrenal medulla
Preganglionic neuron.
Parasympathetic
(pre-postganglionic)
Sympathetic
postganglionic nerve
endings (sweat glands
& skeletal muscle).

104. Nicotinic Receptors
• Located in the ganglia of both the
PSNS and SNS
• Named “nicotinic” because can be stimulated
by the alkaloid nicotine

105. 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

106. Parasympathetic (Cholinergic) Drugs

107. Subdivisions of the Autonomic Nervous System
Sympathetic Parasympathetic
Primary
Neurotransmitter
norepinephrine
epinephrine (~20%)
acetylcholine
Receptors
&
Second
Messenger
Systems
Adrenergic GPCRs
α1 – IP3/DAG, ↑[Ca2+
]i ↑PKC
α2 - ↓cAMP/PKA
β1 - ↑cAMP/PKA
β2 - ↑cAMP/PKA
β3 - ↑cAMP/PKA
Muscarinic GPCRs
M1 – IP3/DAG, ↑[Ca2+
]i ↑PKC
M2 – ↓cAMP/PKA, ↑PI(3)K
M3 – ↓cAMP/PKA,
IP3/DAG, ↑[Ca2+
]i ↑PKC
M4 –
M5 – IP3/DAG, ↑[Ca2+
]i ↑PKC
Adrenal Medulla
(epi:norepi::80:20)

108. Comparison of sympathetic and
Parasympathetic Pathways
• Neurotransmitters
• Receptors

109. 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.

110. Cholinergic Agents
• Drugs that stimulate the parasympathetic
nervous system (PSNS).
• Drugs that mimic the effects of the PSNS
neurotransmitter
• Acetylcholine (ACh)

111. 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.

112. 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.

113. Parasympatholytic drugs
Muscarinic like action
blockers
Ganglion blockers Neuromuscular blocker
These drugs block the
action of Ach at
cholinergic receptors by
blocking the action of
Ach at muscarinic
receptors
These drugs block the
action of Ach at nicotinic
recpotors
These drugs block the
nicotinic like action of Ach
at neuromuscular junction.
e.g.-
AtropineHomatropine
Hyoscine
e.g.
-Nicotine in large doses.
- Arfonad
- Hexamethonium
e.g.
- curare
Mechanism of action-
competitive inhibition
Competitive inhibition.
-Persistent depolarization
Competitive inhibition.
Clinical use:
Atropine used for:--
dilation of pupil- relive
spasm- prevent
bronchial secretion
- Ganglion blocker used
for blocking conduction in
sympathetic ganglion of
hypertension.
- Curare is used as a
muscle relaxant

114. Sympathetic (Adrenergic) Drugs

115. DHBR
NADP+
NADPH
from phe, diet, or protein
breakdown
Tyrosine L-Dopa
H2OO2
Tyrosine hydroxylase
(rate-determining step)
BH2BH4
1
Dopa
decarboxylase
CO2
Dopamine
pyridoxal
phosphate
2
Dopamine hydroxylase
ascorbate
H2O
Norepinephrine
O2
3
PNMT
SAM SAH
Epinephrine
4
Biosynthesis of catecholamines. BH2/BH4, dihydro/tetrahydrobiopterin; DHBR,
dihydrobiopterin reductase; PNMT, phenylethanolamine N-CH3 transferase; SAH, S-
adenosylhomocysteine; SAM, S-adenosylmethionine
Parkinson’s disease: local
deficiency of dopamine
synthesis; L-dopa boosts
productionPNMT specific to
adrenal medulla
SAM from
metabolism of
Met
DPN OHase in neuro-
scretory granules

116. ........
acetylcholine
Adrenal Medulla
Chromaffin Cell
Neuron
Acute
regulation
Tyrosine
L-Dopa DPN
DPN
↓
NE
granule
induction
Chronic
regulation
Stress
Hypothalamus
ACTH
Cortisol
from adrenal
cortex via intra-
adrenal portal
system
Epinephrine
PNMT
NE
neuro-
secretory
granules
E E E
NE E
Regulation of the release of
catecholamines and synthesis of
epinephrine in the adrenal
medulla chromaffin cell.
promotes
exocytosis
⊕
................
E
EE
ENE
E
E E
NE
E
Ca2+

117. Norepinephrine
Epinephrine COMT + MAO
Vanillylmandelic acid
Degradation of epinephrine, norepinephrine and dopamine via
monoamine oxidase (MAO) and catechol O methyl-‑ ‑
transferase (COMT)
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.
Dopamine Homovanillic acid
COMT + MAO

118. Table 1. Classification of Adrenergic Hormone Receptors
Receptor Agonists
Second
Messenger
G protein
alpha1
(α1
) E>NE IP3
/Ca2+
; DAG Gq
alpha2
(α2
) NE>E ↓ cyclic AMP Gi
beta1
(β1
) E=NE ↑ cyclic AMP Gs
beta2
(β2
) 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

119. NH2
HOOC
Figure 4. Model for the structure of the β2-adrenergic receptor

120. 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)
Process
α1
-receptor
(IP3
, DAG)
α2
-
receptor
(↓ cAMP)
β1
-
receptor
(↑ cAMP)
β2
-receptor
(↑ cAMP)
Carbohydrat
e
metabolism
↑ liver
glycogenolysis
No effect No effect
↑liver/muscle
glycogenolysis;
↑ liver gluconeogenesis;
↓ glycogenesis
Fat
metabolism
No effect ↓ lipolysis ↑ lipolysis No effect
Hormone
secretion
No effect
↓ insulin
secretion
No effect
↑ insulin and glucagon
secretion
Muscle
contraction
Smooth
muscle - blood
vessels,
genitourinary
tract
Smooth
muscle -
some
vascular;
GI tract
relaxation
Myocardial
-↑ rate,
force
Smooth muscle
relaxation - bronchi,
blood vessels,
GI tract, genitourinary
tract

121. ⊕
β1 or β2
receptor
ATP cyclic AMP
Gs
β
γ
αs
β
γ
GTP
inactive
adenylyl
cyclase
γ
β
GTP
ACTIVE
adenylyl
cyclase
inactive
adenylyl
cyclase
α2 receptor
Figure 5. Mechanisms of β1, β2, and α2 agonist effects on adenylyl cyclase activity
Gi
β
γ
αi
GTP
αs
GTP
αi
X


122. "FIGHT OR FLIGHT" RESPONSE
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).
epinephrine:
rapidly mobilizes fatty acids as the primary fuel for muscle action
increases muscle glycogenolysis
mobilizes glucose for the brain by ↑ hepatic glycogenolysis/
gluconeogenesis
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
secretion.

123. OH OP
[2]
degradation
to VMA
insulin activation of protein
phosphatase to dephosphorylate
enzymes[7]
α
[5]
γ
β
GTPase
αGDP
epinephrine
phosphorylation
of β-receptor by
β-ARK decreases
activity even with
bound hormone
OH OH
[3]
OP OP
[4]
OPOP
binding of β-arrestin
further inactivates
receptor despite
bound hormone
AC
cAMPATP
activated PKA
phosphorylates
enzymes
[6]
AMP
phosphodiesterase
GTP
[1]
dissociation
Figure 6. Mechanisms for terminating the signal generated by epinephrine
binding to a β-adrenergic receptor

124. Β1 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
Α1 receptors are found most commonly in sympathetic target tissues
A2 receptors are found in the GI tract and pancreas (relaxation)