2. Homeostasis
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.
The nervous system with the endocrine system
controls and coordinates various functions of the body.
3. Classification of nervous system
Anatomical
Central nervous system
Brain and spinal cord
Peripheral nervous system
Motor and sensory nerves
Physiological
Motor nervous system
Somatic nervous system
Autonomic nervous system
Sensory nervous system
Integrative nervous system
4. Peripheral Nervous
System
• Sensory Nerves
(to the brain)
Carry messages from
receptors in the internal
and external sense organs
to the spinal cord and then
to the brain
• Motor Nerves
(from the brain)
Carry orders from CNS to
muscles, glands
5. Somatic nervous system provides voluntary
motor control of skeletal muscle.
Autonomic nervous system provides an
involuntary control of internal environment and
viscera.
Motor nervous system
7. Somatic nervous
system
Autonomic Nervous
system
General functions Adjustment to external
environment
Adjustment within internal
environment
Center Anterior Horn cells Lateral Horn cells
Numbers of
neurons
1 2
Ganglia outside
the CNS
no Sympathetic Chain ganglia,
collateral ganglia or terminal
ganglia
Effectors Voluntary muscle Cardiac muscle glands, smooth
muscle
Neurotransmitter Acetylcholine
Acetylcholine or adrenaline &
noradrenaline
Comparison
8. The ANS is part of the peripheral
nervous system and it controls many
organs and muscles within the body.
It is involuntary, acts in a reflexive
manner.
Autonomic nervous system
9. The ANS is most important in two situations:
1- In emergencies that cause stress and require
us to "fight" or take"flight" i.e.sympathetic
2- In no emergencies that allow us to "rest" and
"digest". i.e.parasympathetic
10. • 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
postganglionic neuron targetPreganglionic neuron
from CNS
autonomic ganglion
outside CNS
Sympathetic and parasympathetic
Nervous Systems
11.
12. 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.
Interneuron Present Absent
Effector
Organ
Smooth , Cardiac
Muscles
Skeletal
19. 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 or
receptors
Target tissues are
smooth muscle, cardiac
muscle, endocrine
glands, brown fat
20. Sympathetic System: Preganglionic Cell Bodies
intermediolateral
gray columns
lateral
horn
Clinical Relevance
» dysfunction due to cord injury
21. Sympathetic 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
22. Sympathetic 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
23. Sympathetic System: Summary
T1
L2
4- somatic
tissues
(body wall, limbs)
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
visceral tissues
(organs)
1- Cervical division
24. 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 effector
organs.
T1-T2
25. Effects of cervical division
EYE: pupil dilatation (mydriasis), 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.
26. (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.
27. (2) Cardiopulmonary division
Heart:
Increase all properties of cardiac muscle
contractility, rhythmicity, excitability,
conductivity.
Coronary vessels: sympathetic supply at first causes
vasoconstriction, and then it causes vasodilatation
due to accumulation of metabolites.
Bronchi: Broncho dilatation, decrease bronchial
secretions and vasoconstriction of pulmonary blood
vessels.
28. 3- Sympathetic Pathways to the Abdominal Organs
(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 divide into
two branches:
(1)Greater splanchnic nerve
(2)Lesser splanchnic nerve.
29. Greater splanchnic nerve
Origin: Preganglionic nerve fibers emerge from
lateral horn cells of lower six thoracic segments
and then relay in the collateral ganglia (celiac,
superior mesenteric and inferior mesenteric
ganglia) in the abdomen.
Course: Postganglionic nerve fibers supply the
abdominal organs .
30. Greater splanchnic nerve
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 noradrenaline.
31. Lesser splanchnic nerve
Origin: Preganglionic nerve fibers originate from the
lateral horn cells of the 12th thoracic and upper two
lumber segments.
Course: 2 nerves from both sides unite together
forming the presacral nerve, which proceeds to
pelvis and divides into two branches (2
hypogastric nerves), then relay in the inferior
mesenteric ganglion.
Postganglionic nerve fibers supply the pelvic viscera:
32. 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.
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.
Lesser splanchnic nerve (continue)
33. 4- somatic
division
(body wall, limbs)
postganglionics
via 31 spinal nerves
to somatic tissues of neck,
body wall, and limbs
sympathetic
trunk
34. (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 join the spinal nerves to the somatic tissues.
36. Somatic division
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.
Muscles during exercise: V.D causing delayed fatigue and early
recovery.
37. Fig. 45.34(TE Art)
Blood flow to Stomach
skeletal muscles contractions
increases are inhibited
Hypothalamus activates
sympathetic division of
nervous system
Heart rate, blood pressure,
and respiration increase
Adrenal medulla
secretes
epinephrine and
norepinephrine
38. The Role of the Adrenal Medulla in
the Sympathetic Division
• Major organ of the sympathetic nervous
system
• Secretes great quantities 80%epinephrine
and 20% norepinephrine)
• Stimulated to secrete by preganglionic
sympathetic fibers
40. "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.
43. Parasympathetic
Sometimes called the “cranio-
sacral division
Long preganglionic neurons;
short postganglionic neurons
(often in the target organ)
Preganglionic neurons secrete Ach
on nicotinic receptors
Postganglionic neurons secrete Ach
on muscarinic receptors
Target tissues are smooth muscle,
cardiac muscle, exocrine glands,
brown fat
44. Actions of Parasympathetic
Any gland ( secretion )
Any smooth muscle ( contraction )
Any blood vessel ( Vasodilatation )
Heart ( inhibition )
Friend of GIT
45. Parasympathetic Pathways
Cranial outflow
• CN III, VII, IX, through four ganglia
supply head
• Vagus nerve (CN X) is major
preganglionic parasymp. supply to
thorax & abdomen
• Synapse in ganglia within
wall of the target organs .
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
46. 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
60. 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
61. Oculomotor Nerve
CN III
Origin: Edinger-Westphal
nucleus at midbrain.
Course:
preganglionic from E-W
nucleus to rely in the
ciliary ganglion.
Postganglionic supply:
o pupillconstrictor
muscle-----miosis
o ciliary muscle----
accommodation to
neat vision
o 4 extraocular muscles-
-----movements of the
eye ball.
62. Effects of cutting oculomotor
nerve
Mydriasis
( paralysis of constrictor pupilae muscle)
Loss of accomodation of eye for near
vision ( paralysis of ciliary muscle )
Latent squint & diplopia
( paralysis of medial rectus muscle )
Ptosis
( paralysis of levator palpebrae Superioris )
63. CN VII:
Facial Nerve
• Motor: muscles of facial
expression
• Sensory: innervation of face
Taste
• Reflexes: corneal reflex
64. CN VII
Facial Nerve
Origin: The superior salivary nucleus in pons.
Course:
Preganglionic nerve fibers run in the chorda tympani
relay in Submaxillary ganglion
Postganglionic nerve supply
submandibular and sublingual salivary glands
and anterior 2/3 of the tongue.
Preganglionic nerve fibers
Relay in Sphenopalatine ganglion.
Postganglionic nerve supply
the mucosa of the soft palate and nasopharynx
secretory to Lacrimal glands.
65. Relay
Submandibular ganglion
( chorda tympani fibers) to supply submandibular
&sub lingual salivary glands
Sphenopalatine ganglion
to supply lacrimal & nasal glands
Functions
Secrotory and VD to submandibular and
sublingual salivary glands watery saliva large in
volume little in enzyms
Secrotory and VD to nasal and lacrimal glands
VD to anterior 2/3 of tongue
CN VII
Facial Nerve
66. CN IX: Glossopharyngeal Nerve
Sensory and motor
innervation of structures of
the tongue and pharynx
Taste
67. CN IX: Glossopharyngeal Nerve
Origin: inferior salivary nucleus (at junction of the
pons and medulla
Relay : otic ganglion.
Course: Postganglionic nerve fibers arise
from otic ganglion supply:
• the parotid salivary gland
• posterior 1/3 of the tongue
Actions:
Secrotory and VD to parotid gland
VD to posterior 1/3 of tongue
68. CN X
Vagus Nerve
• A mixed sensory and
motor nerve
• Main parasympathetic
nerve
– “Wanders” into thorax and
abdomen
69. CN X: Vagus Nerve
Origin: Dorsal vagal nucleus in medulla oblongata
Course: from dorsal vagus nucleus to terminal
ganglia that supply abdominal viscera
70. Thorax
HEART: The vagus nerve supplies both atria and don't
supply the ventricles (and this called vagus escape
phenomena).
Inhibition of all atrial properties (lead to bradycardia)
Reduction of O2 consumption by cardiac muscle.
Coronary vasoconstriction (indirect )
71. • Lungs: Vagus stimulation causes:
• Bronchoconstriction.
• Increased bronchial secretion.
• Vasodilatation of pulmonary blood vessels.
• These responses lead to precipitation of
asthma.
72. Abdomen
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 digestion of foods.
Secretory to GIT glands (stomach, duodenum, liver and
pancreas)
VD of gastric blood vessels
73. Gall bladder:
Vagus stimulation causes:
Contraction of the gall bladder wall.
Relaxation of its sphincter.
These responses lead to evacuation of
the gall bladder.
74. Sacral Outflow
(to pelvis)
Origin: Preganglionic nerve fibers arise from the
lateral horn cells of the 2nd, 3rd and 4th sacral
segments.
Relay : terminal ganglia
75. Urinary bladder:
parasympathetic stimulation causes:
- Contraction of the bladder wall
- Relaxation of its sphincter.
- These responses lead to micturition.
76. Rectum and descending colon:
parasympathetic stimulation causes:
- Contraction of its wall.
- Relaxation of internal anal sphincter.
- These responses lead to
defecation.
77. Seminal vesicles and prostate:
parasympathetic stimulation causes:
- Secretion of these glands.
Erectile tissue:
parasympathetic stimulation causes:
- Vasodilatation which lead to erection.
79. Sympathetic N.S. Parasympathetic N.S.
Like the accelerator of
your car
Mobilized the body for
action
Preganglionic ,trohs :
nihtiw espanysehtlaretal&
laretallocailgnag
Postganglionic :gnol
Has a wide distributions
Like the brakes in your car
Slows the body down to
keep its rhythm
Enables the body to conserve
and store energy
Preganglionic: long, synapse
within the terminal ganglia
Postganglionic: short
Has a restricted distributions
Like the accelerator of
your car
Mobilized the body for
action
Preganglionic: short,
synapse within the lateral &
collateral ganglia
Postganglionic: long
Has a wide distributions
80. 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
83. Parasympathetic
Neurotransmitters
ACh, +
NE (ACh at sweat glands),
+ / -, α & ß receptors
ACh, + / -
muscarinic receptors
• Parasymp. postgangl. Ach
• excitatory (+) or inhibitory (-)
• Symp. postgangl. (NE) & are
excitatory (+) or inhibitory (-)
Sympathetic
ACh, +
• All preganglionics release
acetylcholine & are
excitatory (+)
84. Target Tissues
Parasympathetic
•Organs of head, neck,
trunk, & external genitalia
Sympathetic
•Organs of head, neck,
trunk, & external genitalia
• Adrenal medulla
• Sweat glands in skin
• Erector muscles of hair
• ALL vascular smooth muscle
» Sympathetic system is distributed to essentially all
tissues
» Parasympathetic system never reaches limbs or
body wall (except for external genitalia)
85. Sympathetic supply is much wider in
distribution than parasympathetic which
doesn’t supply the visceral structures in the limbs
, skin & thoracic and abdominal walls .
Many tissues have double supply by both
systems , one of them may be dominent e.g.
vagus tone on the heart
Many tissues are supplied by one system
86. Tissues supplied by sympathetic only
- skin structures:
blood vessels
Sweat glands
pilomotor muscle
blood vessels of skeletal Muscles
Adrenal medulla.
Cardiac muscles of both ventricles
Dilator pupille muscle
Splenic capsule
Ileocecal valves
87. Tissues supplied by para sympathetic only
Constrictor pupillae muscle
Eosophageal muscles
Gastric and pancraetic exocrine glands
88. The parasympatheticsystem is anabolic
and energy storing
It preserves energy and helps recovery and
repair through :
Inhibition of the heart to save its energy
during rest and sleep.
Stimulation of the gastro intestinal
secretions and motility to supply the tissues
with nutrients and energy stores.
89. Sympathetic system is a catabolic system that acts
as one unit to prepare the body for increased
activity during emergency states as fight , fight , fair
, exposure to cold , muscle exercise , hemorrhage ,
hypotension , hypoglycemia , anaesthesia , emotions
, …. Etc .
Sympathetic system induces lipolysis and liver
glycogenolsis.
90. Both systems are usually antagonistic in
function.
When one system is stimulated the other is
inhibited ( reciprocal relation )
91. In some conditions both systems are stimulated at
the same time :
Salivary secretion : under normal condition is large in
volume ( parasympathetic ) and rich in enzymes and
organic substances ( sympathetic )
Weeping: lacrimation (parasympathetic) & emotions
(sympathetic).
During sexual intercourse :
erection is parasympathetic
while increase heart rate is sympathetic
94. Synapses
The synapse is the relay point where information is
conveyed from neuron to neuron by chemical
transmitters.
The axon terminal 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 synaptic cleft that separates the
membranes of presynaptic and postsynaptic
neurons.
95. 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.
96. 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
97.
98. 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
Removal of the chemical transmitter
99. In the sympathetic nervous system the
chemical transmitter is
(adrenaline,noradrenaline) or
(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.
100. Acetylcholine
Important neurotransmitter in central and
peripheral nervous systems.
Acetylcholine is synthesized in the
nerve terminal.
Acetyl-coenzyme A (acetyl CoA) is
manufacured in mitochondria.
Choline is synthesized in the terminals by
active reuptake from interstitial fluid.
acetyl CoA + choline = acetylcholine.
101.
102. Acetylcholine storage
Acetylcholine is stored in vesicles in the
nerve terminal after its synthesis, each
vesicle contains approximatly 104 Ach
molecules, which are released as a single
packet.•
103. In synaptic cleft, Acetylcholinesterase
breaks it down into acetate and choline.
50% of choline is reuptaken into
presynaptic neuron.
Acetylcholine inactivation
104. Acetylcholine release
The arrival of the action potential to the
nerve terminal, increases the permeability
of the terminal to Ca++ influx.
Ca++ releases the synaptic vesicles from
synapsin (that normally binds the vesicles)
,this unbinding causes vesicles to sweep
and attach to the presynaptic membrane.
The vesicles rupture and the acetylcholine is
released in the synaptic cleft and acts on its
specific receptors on the postsynaptic
membrane.
105. To localize the action of acetyl
choline
If not destructed generalized
parasympathetic effect will occurs
which will be harmful or even fetal
a) Heart inhibition
b) Lung broncho constriction
Functions of choline estrases
106. Acetylcholine release sites
Central cholinergic fibers :
Preganglionic nerve fibres of both sympathetic and
parasympathetic divisions of the autonomic nervous
system.
Autonomic ganglion to the adrenal gland.
Neuromuscular junction.
Peripheral cholinergic fibers :
Postganglionic nerves of the parasympathetic
division.
The sympathetic innervation of sweat glands and
vasodilator fibers to skeletal Muscles ( sympathetic
cholinergic fibers )
108. Acetylcholine receptors
Two types of cholinergic receptors are well
known:
Nicotinic receptors which are easily activated by
agonist molocule such as nicotine
Muscarinic receptors: which are sensitive to
muscarine.
109. Cholinergic receptors
Peripheral Muscarinic
cholinergic receptors
Central Nicotinic
cholinergic
receptors
M1(brain), M2 (cardiac), M3
(glandular&smooth muscle) M4
(pancreas).M5.
Two types:-
Ganglionic - Neruomuscular
Types
Muscarine, Ach, carbarcholineNicotine in small doses,
Ach, metacholine
Stimulated
by
AtropineNicotine in large dosesBlocked by
- All Postganglionic Parasympathetic
-postganglionic Sympathetic nerve
endings (sweat glands & skeletal
muscle).
- autonomic ganglia ,
- adrenal medulla and
- motor end plates of
skeletal muscles
.
site
110. Nicotinic Receptors
• Located in the ganglia of both the PSNS
and SNS
• Named “nicotinic” because can be
stimulated by the alkaloid nicotine
111. Muscarinic Receptors
• Located peripherally ) postganglionic
cholinergic fibers )
– Smooth muscle
– Cardiac muscle
– Glands of parasympathetic fibers
– Effector organs of cholinergic sympathetic
fibers
• Named “muscarinic” because can be
stimulated by the alkaloid muscarine
113. DHBR
NADP+
NADPH
phenylephrine
hydroxylase
In liver
Tyrosine L-Dopa
H2OO2
Tyrosine hydroxylase
(rate-determining step)
BH2BH4
1
CO2
Dopamine
Dopa
decarboxylase
pyridoxal
phosphate
2
Dopamine hydroxylase
ascorbate
2H O O2
3
SAM SAH
4
Parkinson’s disease: local
deficiency of dopamine
synthesis; L-dopa boosts
production
Epinephrine
PNMT specific to
adrenal medulla
SAM from
metabolism of
Met
Norepinephrine
PNMT
115. Removal of noradrenaline
1) Active reuptake
Into adrenergic nerve endings ( Removal of 50-80% )
2) Diffusion away
To surrounding body fluids and then into blood
3) Destruction by Enzymes as
Mono amino oxidase ( MAO )
By Oxidation to form Dihydroxymandelic acid
Catechol-o-methyl-transverase ( C.O.M.T )
By methylation to form normetanephrine then oxidation
by MAO to form valinyle mandelic acid
117. M.A.O C.O.M.T
1) Outer surface of
mitochondria
2) Adrenergic nerve fibers
3) Brain
4) Liver
5) Kidneys
Act by oxidation
Present diffusely in all
tissues but not found in
adrenergic nerve endings
Act by methylation
118. Adrenergic receptors
Sites
Post ganglionic sympathetic fibers
(Surface of effecter organs) except
Sweat glands
Blood vessels of skeletal muscles
Membranes of the post ganglionic nerve
ending ( Pre synaptic receptors )
119. Mechanism of action of
catecholamines
Catecholamines act on:
Beta receptors: by stimulating adenyle
cyclase & intracellular cAMP
Alpha1 receptors: by increasing
intracellular calcium
Alpha2 receptors: by inhibiting adenyle
cyclase & intracellular cAMP
120. Table 1. Classification of Adrenergic Hormone
Receptors
Receptor Agonists
Second
Messenger
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
121. Alpha receptors: mainly excitatory except in the
intestine.
Beta receptors : mainly inhibitory except in the heart.
Alpha1 receptors are present mainly on the
postsynaptic nerve endings.
Alpha2 receptors are present mainly on the presynaptic
nerve endings.
Alpha 2 receptors in gastrointestinal wall and islets of
langerhans of pancreas produce inhibitory effects.
122. 1 found on heart muscle and in certain cells of the kidney
B2 found in certain blood vessels, smooth muscle of airways
1 receptors are found most commonly in sympathetic target tissues
A2 receptors are found in the GI tract and pancreas (relaxation)
123. Adrenaline and noradrenaline act on both alpha and beta
receptors
Adrenaline acts equally on both receptors
Noradrenaline stimulate alpha more than beta
Adrenaline and noradrenaline act equally on beta1
receptors
Adrenaline is stronger beta2 stimulant than
noradrenaline
124. 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
1-receptor
(IP3, DAG)
2-
receptor
( cAMP)
1-
receptor
( cAMP)
2-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
125. 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
126.
1 or 2
receptor
ATP cyclicAMP
Gs
s
GTP
inactive
adenylyl
cyclase
GTP
ACTIVE
adenylyl
cyclase
inactive
adenylyl
cyclase
2 receptor
Figure 5. Mechanisms of 1, 2, and 2 agonist effects on adenylyl cyclase activity
Gi
i
GTP
s
GTP
i
X
127. OP
[2]
degradation
to VMA
insulin activation of protein
phosphatase to dephosphorylate
enzymesOH [7]
[5]
GTPase
GDP
epinephrine
phosphorylation
of -receptor by
-ARK decreases
activity even with
bound hormone
OH OH
[3]
OP OP
[4]
OPOP
binding of -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 -adrenergic receptor