Far Eastern University – Nicanor Reyes Medical Foundation
Physiology A – Autonomic Nervous System (Parts 1 and 2)
Dra. Valerio (2015)
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AUTONOMIC NERVOUS SYSTEM
 Division or branch of nervous system involved in homeostasis
(maintenance of the constancy of internal environment of the
body)


Main function: to regulate visceral function or functions of
different visceral internal organs
 Regulation of cardiovascular function
 Regulation of respiratory function
 Regulation of gastrointestinal function
 Regulate secretions of different exocrine glands (including
sweat glands and salivary glands
Basically, all functions of the internal organs are regulated by
the autonomic nervous system
Main Division of Human Nervous System:
 Two divisions working together; PNS is connected to CNS

Olfactory
Optic
Oculomotor
Trochlear
Trigeminal
Abducens
Facial
Acoustic / Vestibulocochlear
Glossopharyngeal
Vagus
Spinal accessory nerve
Hypoglossal
31 pairs of Spinal Nerves
 Originated from the different segments of the spinal
cord
Cranial Nerves associated with the autonomic nervous system
 3 (Oculomotor)
 7 (Facial)
 9 (Glossopharyngeal)
 10 (Vagus)
Spinal Nerves associated with the autonomic nervous system
 Thoracic (T1-T12)
 Lumbar (L1-L3)
 Sacral (S2-S4)
Nervous System
 Can regulate body functions by means of reflex arc or reflex
activity
1.
Central Nervous System
 Different Parts of the Brain
O Cerebral cortex
O Hypothalamus
O Thalamus
O Basal ganglia
O Cerebellum
O Brainstem (midbrain, pons, and medulla)
 Different Segments of the Spinal Cord
O Cervical (8 pairs)
O Thoracic (12 pairs)
O Lumbar (5 pairs)
O Sacral (5 pairs)
O Coccygeal (1 pair)
2.
Peripheral Nervous System
 12 pairs of Cranial Nerves
 Originated from the nuclei located in the brainstem
(midbrain, pons, and medulla)
Page 1 of 15
Five components of a Reflex arc:
1. Sensory receptor
2. Afferent Nerve
3. Center
4. Efferent Nerve
5. Effector
Sensory receptor
 Specialized structures located in almost all parts of the body
stimulated by changes inside or outside the body
 Body surface: walls of blood vessels, walls of different internal
organs, skin, muscle, intestinal wall, heart muscle wall
Examples:
O Plasma: Osmoreceptors
O Muscles (muscle spindles): Proprioreceptors
 Stimulated by the movement of limbs and extremities
during stretching
O Skin: Thermoreceptors
 Stimulated by the changes in temperature
O Eyes (rods and cones): Photoreceptors
 Stimulated by changes in wavelength of light
O Mouth: Chemoreceptors
 Stimulated by changes in chemical composition of
food
O Arterial Wall: Baroreceptors
 Stimulated by stretch of arterial wall during increase
of blood pressure
O Intestinal Wall: Mechanoreceptors
 Stimulated by painful segments in the intestine
causing stretching of intestinal wall (retained foods)
 Initially, when a receptor is stimulated, it will generate a local
potential or generator / receptor potential
 When it reaches Critical Firing Level or the threshold voltage, it
is then converted into action potential or sensory impulse
 It will then be transmitted by an afferent nerve to the center
Examples of a Reflex Activity:
Afferent Nerve
 A sensory nerve that transmits the sensory impulses from
sensory receptors to the center
Center
 The brain and the spinal cord
 Interpret and analyze the sensory impulse transmitted to it
 Generate another type of action potential which is now a
motor impulse to be transmitted by an efferent nerve to the
different effector cells/ effector organs in the body
Efferent nerve
 Motor nerve that transmits motor impulses from the center to
the effector cell
Effector cell
 Receives and perform the action dictated by the motor impulse
 Four types of effector cell:
O Skeletal / Striated Voluntary Muscle present mostly on
the body surface attached to tendon
O Cardiac Muscle in the heart
O Smooth muscle in the wall of the viscera
O Glands
Page 2 of 15

In the walls of the intestine, the mechanoreceptors are
stimulated because of retained food. They will generate
sensory impulse transmitted by an afferent nerve to the spinal
cord which is the center. The center will then generate a motor
impulse transmitted by an efferent nerve back to the intestinal
wall (smooth muscle) causing contraction or intestinal motility
that will push the food to the anal direction.

Food in the mouth, chemical components of the food will
stimulate the chemoreceptors present in the taste buds. These
receptors will generate an action potential transmitted by n
afferent nerve to the medulla which is the center. From the
medulla, a motor impulse is generated transmitted by an
efferent nerve from the salivary glands which are the effectors.
These effectors will increase the production of saliva.
Peripheral Nervous System
 Spinal nerve and cranial nerve are made up of bundle of nerve
fibers
 Four types of muscle fibers:
O Somatic afferent
 Sensory nerve that will transmit sensory impulses
from sensory receptors (head, body walls,
extremities) going to the center
O Somatic efferent
 Motor nerve that transmits motor impulses from the
center to the effector cell (skeletal striated or
voluntary muscle only)
O Visceral afferent
 Sensory nerve that transmits sensory impulses from
sensory receptors (located from the wall of the
viscera) to the center
O Visceral efferent
 Motor nerve that transmits motor impulses from the
center to effector cells (cardiac muscle cells, visceral
smooth muscle cells, and glands)
Two Main divisions of the Peripheral Nervous System
 made up of cranial nerve originating from the brainstem and
spinal nerve originating from the spinal cord
1. Somatic nervous system
 Somatic afferent
 Somatic efferent
2. Autonomic / Visceral Nervous System
 Visceral afferent
 Visceral efferent
Somatic NS
Autonomic NS
Operates under conscious level
Operates under subconscious level
Voluntary
Involuntary
Deliberate response
Orients on external environment (main
function is to bring about movement
and locomotion)
Receptors in the head, body wall,
extremities
Center: Cerebral Cortex (basal ganglia,
cerebellum, and spinal cord to a lesser
extent)
NEUROMUSCULAR
JUNCTION
Transmission of motor
impulses from a somatic
efferent nerve ending to
the skeletal muscle cell
membrane (MOTOR END
PLATE:
End
Plate
Potential)
NTA Utilized (biochemical
in
nature):
ACETYLCHOLINE
Autonomic NS
Effector cell: visceral smooth muscle,
cardiac muscle, and glands
TWO NEURON FIBER EFFERENT NERVE
Coming from the center (spinal cord/
brainstem) efferent nerve will form
synapse with a PERIPHERAL GANGLION
(neuron found outside the brain/ spinal
cord or simply outside the CNS):
PREGANGLIONIC FIBER- cell body is
located in the center from the
peripheral ganglion, efferent nerve will
form synapse with the membrane of
the effector cell: POSTGANGLIONIC
FIBER- cell body is located in the
peripheral
ganglion
NEUROEFFECTOR JUNCTION
NTA Utilized (biochemical in nature):
ACETYLCHOLINE
AND
NOREPINEPHRINE
SOMATIC EFFERENT NERVE
Automatic/ Instantaneous response
Regulates visceral functions (internal
organs; play role in maintaining the
balance or homeostasis in the internal
environment)
Receptors in different visceral internal
organs
Center: Hypothalamus, brainstem, and
spinal cord
Note: In the autonomic nervous system, few are controlled by the cerebral
cortex, thus mostly involuntary, partly voluntary
O Respiration: voluntary when holding your breath but only at a certain
point because O2 will not enter causing a decrease in pO2 (stimulates
peripheral chemoreceptor that will also transmit impulses in the
respiratory center in the medulla) and increase in pCO2 (stimulates
respiratory center in the medulla) respiratory center is automatic
so whether you like it or not, you will still breathe
O Micturition: autonomic reflex if there is an increase in volume in the
urinary bladder (stretching)  detrusor muscle
O Defecation: when rectal pressure reaches 18mmHg (urge to defecate)
but can resist voluntarily (external anal sphincter: contraction is in
voluntary control); 55 mmHg (maximum: automatic)
Page 3 of 15
Somatic NS
Effector cell: skeletal/
striated
or
voluntary
muscle
ONE
NEURON
FIBER
EFFERENT NERVE
AUTONOMIC EFFERENT NERVE
QUESTIONS:
How can you differentiate an NTA from a hormone which are both
skeletal mediators?
 NTA are synthesized and stored temporarily at a nerve
ending while Hormones are synthesized and stored
temporarily in secretory cell or endocrine gland
 NTA are released only either on NMJ or NEJ (localized;
needs action potential to release) while Endocrine
hormones are released on the blood (paracrine
hormones – interstitial fluid only)
How can you differentiate Norepinephrine from Epinephrine?
 Norepinephrine is both an NTA and a hormone (can be
synthesized and stored at nerve endings and can also be
synthesized, stored, and release by the adrenal medulla
which is an endocrine gland) while Epinephrine is a
hormone that can be secreted by the adrenal medulla
but cannot be secreted by nerve endings although there
are some brain cells which can secrete epinephrine so it
is MOSTLY a hormone
Somatic NS
Autonomic NS
Site of inhibition: 2 sites
(center and NMJ)
Site of inhibition: 3 sites
(center, peripheral ganglion, and NEJ)
NON AUTOMATIC CELL
 Cannot generate its
own action potential
 Example:
skeletal
muscle
 Undergo complete
paralysis
and
atrophy
Stimulation:
(+) excitation
Respond
always
Contraction
by
AUTOMATIC CELL
 Involuntary
 Has the capability to generate its
own
action
potential
spontaneously independent of
extrinsic nervous stimulation or
autonomic stimulation
 Example: SA node in the heart ,
enteric neuron in GIT
 Automaticity
Stimulation:
(+) excitatory/ inhibitory
Increase/ decrease heart rate,
intestinal motility, pupillary size, and
glandular secretion
Vasoconstriction/ vasodilatation
Bronchoconstriction/bronchodilation
Papillary dilatation/ constriction
AUTONOMIC NERVOUS SYSTEM
 Has three subdivisions:
1. Enteric NS
2. Sympathetic NS
3. Parasympathetic NS
ENTERIC NERVOUS SYSTEM
 nervous system of the GIT (stomach, small intestine, large
intestine, rectum, anus)
 NEURONS present in the walls of GIT:
O MEISSNER’S PLEXUS
 Located in the SUBMUCOSAL layer of GI wall
 Regulates secretory activity of the GIT
Page 4 of 15
O

MYENTERIC
 AUERBACH’S PLEXUS
 Located in the muscular layer of GI wall
 Regulates motor activity of GIT (peristalsis motor
activity)
Activities of enteric are regulated by:
SYMPATHETIC POSTGANGLIONIC FIBERS synapse with enteric
neurons (effector cell: NMJ) inhibits or decreases the activity
of the ENS  indirectly decreasing GIT motor and secretory
activity
PARASYMPATHETIC PREGANGLIONIC FIBERSsynapse with
enteric neurons (peripheral ganglion: NEJ)  increases the
activity of ENS indirectly increasing GIT motor and secretory
activity
ANATOMICAL DIFFERENCES (efferent nerve):
SYMPATHETIC
PARASYMPATHETIC
Origin of Preganglionic Fiber:
Origin of Preganglionic Fiber:
Center: brainstem and spinal
cord
From spinal cord (T1-L3)
THORACOLUMBAR DIVISION
From brainstem (Cranial Nerves)
 3 - Oculomotor
 7 - Facial
 9 - Glossopharyngeal
 10 - Vagus
From spinal cord
 S2
 S3
 S4
T1&T2 – head and neck
(including the radial muscle of
the iris and salivary glands)
T3, T4 & T5 – (plus some nerves
from T1 and T2) thoracic region,
heart, lungs, bronchi

In the abdominal and
pelvic regions, there THREE
additional
COLLATERAL
GANGLIA located before
the vertebral column (PREVERTEBRAL)
:
celiac
ganglion,
superior
mesenteric ganglion and
inferior
mesenteric
ganglion (in front of
vertebral column)
which
innervates
the
submandibular
gland
and
sublingual gland (salivary glands)
Cranial Nerve 9- originates from
the medulla; Glossopharyngeal;
synapse with OTIC GANGLION
which innervates parotid gland
(salivary gland)

Far from the center, in the
effector cell
Cranial Nerve 10 – Vagus
Major parasympathetic nerve
From the medulla which carries
80% of all parasympathetic
effects to the different organs in
the body (heart, lungs, bronchi,
esophagus, stomach, small
intestine, proximal half of LI,
pancreas, liver, gallbladder)
CRANIOSACRAL DIVISION
T6-T12 – neurons Indirectly to
GIT ( stomach, small intestine,
proximal half of large intestine
which are the ascending colon
and transverse colon, liver,
pancreas, gall bladder, spleen
and adrenal medulla, biliary
system)
Sacral Nerve – Pelvic nerve
Distal half of LI, rectum, anus,
genito-urinary system except
kidney
L1-L3 – distal half of large
intestine
which
are
the
descending colon and the
sigmoid, rectum and anus,
genitourinary system including
the kidneys, urinary bladder,
and gonads: together with
superior
cervical
ganglion,
middle cervical ganglion and
stellate ganglion
Length of pre and post
ganglionic fiber:
Length of pre and post
ganglionic fiber:
PRE – short
POST – long
PRE – long
POST – short
T1-L3- vascular wall (blood
vessel) and sweat glands

Almost all visceral organs
receive sympathetic NS
innervations
Location
Ganglion:



of
Peripheral
Near the center, far from
the effector cell
22 pairs of ganglia located
beside
the
vertebral
column where the spinal
cord is
PARAVERTEBRAL
in
location; collectively these
ganglia are referred to as
the SYMPATHETIC CHAIN
(including superior cervical
ganglion, middle cervical
ganglion,
and
stellate
ganglion
which
will
innervate
the
thorax
region-the heart and the
lungs for T1 to L3
Preganglionic fiber)
Page 5 of 15
Location
Ganglion:

of
Peripheral
far from center but near the
effector cell (Cranial nerves
3, 7, and 9)
Cranial Nerve 3 – originates
from the midbrain; Oculomotorsynapses with ciliary ganglion
which innervates post ganglionic
 effector: constrictor muscle
of Iris and ciliary muscle of the
eye (smooth muscles of the eye)
Cranial Nerve 7 – originates
from the pons; Facial; two
ganglia (1) SPHENOPALATINE
GANGLION- which innervates
the nasal and lacrimal glands (2)
SUBMANDIBULAR GANGLION-
Degree of branching
PREganglionic fiber:
of
Degree of branching
PREganglionic fiber:
Reciprocal effect
Reciprocal effect





Extensively branching
More
widespread
or
diffuse/ mass discharge
Example: (1 pre:20 post)

of
Limited branching
More localized except for
the vagus nerve
Example: (1pre:1post)



Almost all visceral organs receive dual innervation (sympathetic
and parasympathetic)
Whenever sympathetic and parasympathetic are present in one
organ, ALMOST ALWAYS they have opposite effects (not
antagonistic because they regulate) but not always
Examples:
 if sympa  heart rate ; parasympa  heart rate
If you cut the vagus nerve innervating the SA node of
heart, there will be tachycardia (sympa  heart rate)
 if sympa  intestinal motility ; parasympa  intestinal
motility
 if sympa causes pupillary dilatation ; parasympa causes
pupillary constriction
 if sympa causes bronchodilatation ; parasympa causes
bronchoconstriction
NEJ- where NTA will mediate transmission of impulses from an
autonomic efferent post ganglionic nerve ending to the
membrane of the effector cell membrane of the visceral
smooth muscle cell, cardiac muscle or glands.
BIOCHEMICAL TRANSMISSION
 Transmission of impulses both in the somatic as well as
autonomic efferent pathways are biochemical in nature or are
mediated by chemical substances called as NTA’s
(Neurotransmitter agents)
 Acetylcholine – cholinergic transmission
 Norepinephrine – adrenergic/ noradrenergic transmission
 Relesead at :
O Somatic neuromuscular junction
O Autonomic peripheral ganglion
O Autonomic neuroeffector junction
BIOCHEMICAL TRANSMISSION
Site of transmission
 In the somatic efferent pathway, NTA released into NMJ:
NMJ – mediate transmission of motor impulses from a somatic
efferent nerve ending to the Nicotinic 1 receptor membrane of
the skeletal muscle cell
 In autonomics, there are two sites where NTA are released
Peripheral ganglion – that will mediate transmission of
impulses from autonomic efferent pre ganglionic nerve ending
to the membrane of the peripheral ganglion
Page 6 of 15
STEP 1: SYNTHESIS AND STORAGE OF NTA
 Take place in vesicles of nerve endings
 When an action potential is generated from the center, it will
be transmitted along an efferent nerve. When this action
potential or motor impulse reaches the nerve ending, there will
be opening of Voltage gated Calcium channels that will allow
Calcium influx. Calcium will initiate synaptobrevin, syntaxin
and SNAP25 that will cause the vesicular membrane to fuse
with the nerve ending membrane causing the release of NTA
agent by exocytosis into the synaptic cleft.
STEP 2: RELEASE OF NTA (AT THE SYNAPTIC CLEFT)
 Once release into the synaptic cleft, the NTA will then bind with
a specific receptor on the membrane of the effector cell.
Therefore, eliciting a physiologic response from the effector
cell.
STEP 3: NTA BINDS WITH RECEPTORS (ON THE EFFECTOR CELL)
 NTA agent will not permanently bind to the receptor
MEMBRANE RECEPTORS FOR NTA
1. IONOPHORES / IONOTROPHIC
 ION CHANNELS (SODIUM LIGAND GATED CHANNELS)
 Nicotinic receptors
 NTA + receptor = opening of Sodium ligand gated channels
 Sodium influx that will depolarize the membrane and will
elicit excitatory response from the effector cell
 Elicit immediate or fast response to effector cell but short
in duration
 Example: acetylcholine when it binds to nicotinic receptor
 Ion sodium channel influx: depolarization (excitation)
 Potassium channel efflux: hyperpolarization (inhibition)
2.
G-PROTEIN COUPLED WITH RECEPTORS
 METABOTROPIC
 Muscarinic and Adrenergic receptors
 Present on the inner surface of the cell membrane
oriented at ICF
 When NTA + receptor on ECF  activate G- protein on ICF
will activate specific intracellular enzymes (ligands) 
lead to formation of Intracellular ligand or second
messenger (cAMP)  mediate action of NTA
 More delayed response for effector cell but long in
duration present even when NTA are deactivated
SECOND MESSENGERS:
 Delayed response but long in duration
 CyclicAMP
 NTA + receptor activating G-protein  stimulate adenyl
nd
cyclase  production of cAMP (2 messenger)  activate
another intracellular enzyme which is protein kinase A 
phosphorylation of specific intracellular enzymes 
stimulation of specific biochemical reaction in the cell
 Mechanism of Cathecolamine (NEP and EP) which bind
with beta receptors and Acetylcholine which bind with
muscarinic receptors
Biochemical Reaction
 Opening of ion channels (calcium and potassium
channels)
 Stimulate protein synthesis
 Stimulate gene transcription
 Change whole metabolic set up of the cell
 REASON WHY G-PROTEIN IS METABOTROPIC (CHANGE IN
METABOLISM OF THE CELL)
 PHOSPHOLIPASE C
 NTA + receptor  (+) G protein  phospholipase c 
breakdown of PhosphoInositol Biphosphate (PIP2) 
Increase Inositol triphosphate (increases Intracellular
nd
Calcium: 2 messenger) and diacylglycerol or DAG
(stimulates (+) Protein Kinase C  phosphorylates specific
Intracellular proteins stimulation again of biochemical
reaction in the cell)
Page 7 of 15

Again Mechanism of Cathecolamine (NEP and EP) which
bind with alpha receptors and Acetylcholine which bind
with muscarinic receptors
STEP 4: DEACTIVATION OF NTA
 After eliciting a physiologic response from the effector cell, it
will be unbound or deactivated/ destroyed
 Mechanisms:
O Enzyme deactivation
Enzymes destroy NTA at the synaptic cleft; deactivate Ach
by acetylcholinesterase that immediately makes short
duration of cholinergic transmission
O Reuptake
NTA is actively transported back to the nerve terminal, but
it will not be enclosed in a vesicle so that the enzyme
present at the nerve terminal will be able to destroy it.
Main mechanism that deactivates NEP will be MAO (Mono
Amine Oxidase) present at nerve terminal. Enzymatic
deactivation is only secondary to reuptake.
O Diffusion away from the synapse
Goes to the circulating blood to the liver and deactivated
by COMT (Cathecol Omethyl Transferase) secondarily for
NEP
CHOLINERGIC TRANSMISSION
 Mediated by Acetylcholine
1. All somatic NMJ (Ach will mediate transmission of motor
impulses from all somatic efferent nerves to the skeletal
muscle cell)
2. All autonomic/ peripheral ganglia (both sympathetic and
parasympathetic)
3. All parasympathetic NEJ (Since parasympathetic nerve
release only to one type of NTA that is Ach:
Parasympathetic NS= Cholinergic division)
4. Sympathetic cholinergic NEJ
 Sweat glands
 Vascular smooth muscles or blood vessels
present in skeletal muscles
NORADRENERGIC TRANSMISSION
 Mediated by Norepinephrine
 All sympathetic adrenergic NEJ (most sympathetic effects to
different effector organs are mediated by NEP;
Sympathetic NS= Adrenergic division
Except sweat glands and smooth muscle cell or blood vessels of
skeletal muscle)
 Cardiac muscle cell, visceral smooth muscle cell, and glands
Efferent Pathway of Somatic Nervous System and the Different
Divisions of the Autonomic Nervous System
SAMPLE EXERCISE 1:
A. SOMATIC NERVOUS SYSTEM
B. PARASYMPATHETIC NERVOUS SYSTEM
C. SYMPATHETIC CHOLINERGIC NERVOUS SYTEM
D. SYMPATHETIC ADRENERGIC NERVOUS SYSTEM
E. ALL
F. B, C AND D
G. B AND C
H. C AND D
I. NONE
1.
2.
3.
4.
5.
Division/s of the Central Nervous system - I
Division /s of the Peripheral Nervous System- E
Involuntary – F
E ffector Cell is the Skeletal Muscle cell- A
Acetylcholine is the NTA released by the preganglionic fibersF
6. Acetylcholine is the NTA released by the postganglionic fiber
to NEJ- G
7. Short pre and long post- H
8. Acetylcholine is the NTA released the NMJ- A
9. Norepinephrine is the NTA released in the NEJ- D
10. With extensive branching of post ganglionic fiber- I
(None because preganglionic fibers are the one branching
out not postganglionic fibers)
Page 8 of 15

AUTONOMICS 2
STEPS IN CHOLINERGIC TRANSMISSION
MEDIATED BY ACETYLCHOLINE
STEP 1: SYNTHESIS OF ACETYLCHOLINE
 Acetylcholine is synthesized from CHOLINNE and ACETYL COENZYME A
 This reaction is catalyzed by the enzyme CHOLINE ACETYL
TRANSFERASE
 Takes place on Nerve endings of:
a. Somatic efferent nerve ending
b. ALL autonomic (sympathetic and parasympathetic)
Preganglionic Nerve Ending
c. Parasympathetic Postganglionic Nerve Ending
d. Sympathetic Cholinergic Nerve Ending
STEP 2: STORED AND RELEASE OF Ach
 Ach will be stored temporarily in vesicles that are located in the
nerve ending so that when an action potential reaches the
nerve terminal, there will be Calcium influx that will facilitate
the release by exocytosis of Ach to the synaptic cleft
STEP 3: Ach BINDING TO SPECIFIC RECEPTORS
 Ach will bind with specific receptors called cholinergic
receptors on the membrane of the effector cells that will elicit
a physiologic response from the effector cell
 Two types of cholinergic receptors:
1. NICOTINIC RECEPTORS
 Ligand gated (ALWAYS EXCITATORY)
 Present in ALL SOMATIC NMJ (membrane of skeletal
muscle cells)
NICOTINIC 1 or “NM RECEPTORS”
 Present also in ALL AUTONOMIC PERIPHERAL
GANGLION
NICOTINIC 2 or “NN RECEPTORS”
2.

MUSCARINIC RECEPTORS
 From small doses of Muscarin poisonG protein
coupled (EXCITATORY/ INHIBITORY)
 Present in ALL Parasympathetic NEJ
 Present also in Sympathetic Cholinergic NEJ (sweat
gland and vascular smooth muscle in skeletal muscle)
 Different visceral organs and glands
Types:
O M1 –mainly in brain; few in stomach
O M2 –abundant in the heart few in visceral smooth
muscles
O M3 –visceral smooth muscles and glands
O M4 –visceral smooth muscles and glands
O M5 –least abundant; present only in specific locations
which will include: sphincter muscle of the iris,
esophagus, parotid gland, and cerebral blood vessels
 M3 and M4: main muscarinic receptors
Page 9 of 15
Difference between Nicotinic and Muscarinic Receptors
NICOTINIC
MUSCARINIC
Purely
PROTEINS; G-PROTEIN
COUPLED
RECEPTOR;
IONOTROPHIC
METABOOTROPIC
When Ach binds with When Ach binds with a muscarinic
nicotinic
receptors receptor in the heart M2 cAMP K
open ligand gated Na efflux
conductance
=
ALWAYS
channels NA influx (HYPERPOLARIZATION)
depolarize
the INHIBITORY
membrane
of
the
effector cell excitary When Ach binds with a muscarinic
receptor in the visceral organs and
response
glands; M3 and M4 INOSITOL
TRIPHOSPHATE (IP3 and DAGas second
messenger) which either  intracellular
Calcium that will elicit EXCITATORY
RESPONSE to effector cells or K efflux
conductance
(HYPERPOLARIZATION)
causing INHIBITORY RESPONSE
Response:
always Response: EXCITATORY/ INHIBITORY but
excitatory
ALWAYS INHIBITORY to the Heart
Contraction of skeletal
muscles;
Facilitation of nerve
impulses from pre to
post ganglionic fibers
STEP 4: DEACTIVATION OF ACETYLCHOLINE
 Deactivated by Acetylcholine esterase present in the synaptic
cleft
 Makes CHOLINERGIC/ PARASYMPATHETIC EFFECTS SHORT IN
DURATION
 Two mechanisms:
a. ENZYME DESTRUCTION/ DEACTIVATION
 Enzyme acetylcholinesterase
 Main mechanism in somatic NMJ, parasympathetic
NEJ, and sympathetic cholinergic NEJ
b. RE-UPTAKE
 Main mechanism in autonomic ganglia
 Ach is deactivated and re-uptake by preganglionic

STEPS IN ADRENERGIC TRANSMISSION
MEDIATED BY NOREPINEPHRINE
STEP 1: SYNTHESIS OF NOREPINEPHRINE
 Biosynthesis:
PHENYLALANINE  initially converted to BETA TYROSINE by the
enzyme phenylalanine hydroxylase  converted to DOPA by the
enzyme tyrosine hydroxylase  converted to DOPAMINE by the
enzyme DOPA decarboxylase  converted to NOREPINEPHRINE by
the enzyme dopamine beta hydroxylase

Happens in the sympathetic adrenergic postganglionic nerve
ending ONLY
 Regulatory Mechanism:
NEGATIVE FEEDBACK
 Regulate the production of DOPAMINE
NOREPINEPHRINE
 Excess dopamine and norepinephrine
 Inhibit the enzyme tyrosine hydroxylase
 Tyrosine will not be converted to DOPA
 Decrease dopamine levels
 Decrease Norepinephrine levels


AND
In the adrenal medulla (SUPRARENAL GLANDS):
 Norepinephrine can be converted into another type of
catecholamine and that is EPINEPHRINE, catalyzed by the
enzyme phenylthinolamine n-methyl transferase
 Conversion does not take place in sympathetic adrenergic
post ganglionic nerve ending but ONLY in the adrenal
medulla
STEP 2: STORAGE AND RELEASE OF NEP
 NEP will be stored temporarily in vesicles
 When an action potential reaches the nerve terminal, there will
be Calcium influx that will facilitate the release of NEP by
exocytosis of Ach to the synaptic cleft. Upon release. NEP as
well as EP will bind with specific receptors on the membrane of
the effector cell
STEP 3: NEP BINDS TO ADRENERGIC RECPTORS
 Types of ADRENERGICI receptors:
O Alpha 1 present in visceral smooth muscles and glands
 NE + alpha1 receptor  IP3/ DAG mostly  Ca
conductance (excitatory) or K conductance
(inhibitory)
 Example of Excitatory:
when NE binds to alpha 1 receptor in radial muscle of
iris  radial muscle will contract that will increase
pupillary size
When NE binds to alpha1 receptor of vascular smooth
muscle contraction of vascular smooth muscle
vasoconstriction
O Alpha 2 present only in nerve terminals of sympathetic
adrenergic postganglionic fiber
 NE+ alpha2 receptor  has negative feedback
mechanism that inhibits release of NEP
O
Beta 1 present only in the HEART
O
Beta 2 also in visceral smooth muscles and glands
 When NE binds with beta2 receptors: RESPONSE IS
MOSTLY INHIBITORY
Example: NE+ beta2 receptor in bronchial smooth
muscle relax and causes bronchodilation (cAMP
and  K conductance = inhibitory)
O
Beta 3 in adipocytes
Page 10 of 15


EXCEPTIONS:
 Alpha receptors in digestive system, bronchial
glands, and pancreatic islets
Response is INHIBITORY (K)
 GI motility and secretion
 Bronchial gland secretion
 pancreatic islet secretion
 Beta 1 receptor in the heart
Response is EXCITATORY (cAMP= Ca)
 heart rate
 force of myocardial infarction
MUSCARINIC
IS PARA INHIBITORY TO THE HEART
WHILE
BETA 1
IS SYMPA EXCITATORY TO THE HEART
There are some sympathetic pre-ganglionic fibers that will
synapse directly with the adrenal medullary cells.
When sympathetic nervous system is stimulated and preganglionic fiber release Ach:
 This Ach will bind with nicotinic 2 receptor present in
the membrane of adrenal medullary cells.
 Adrenal medullary cells are histologically similar to a
sympathetic ganglion
Adrenal medulla as an effector organ can be differentiated with
other effector organs in the body in terms of innervation:
 Adrenal medulla is on PREGANGLIONIC
 Other effector organs are POSTGANGLIONIC
How can adrenal medulla differentiated to sympathetic adrenergic
postganglionic nerve ending:
 Adrenal medulla releases two types of catecholamine: NE
and EP (release into the circulating blood before they
stimulate adrenergic receptors potentiating or reinforcing
sympathetic adrenergic receptors; reason why adrenal
medulla is considered as part of the Sympathetic
Adrenergic Nervous System)
 Sympathetic adrenergic postganglionic nerve ending
secretes NE only (released only on synaptic cleft NEJ)

POTENCY:
 Norepinephrine strongly stimulates alpha and beta 1 receptors
and weakly stimulates beta 2 receptors

Epinephrine strongly stimulates alpha, beta1, and beta 2
receptors (strongly stimulates ALL ADRENERGIC RECEPTORS)

All adrenergic receptors are g-protein coupled receptors; when
NE and EP bind to adrenergic receptor, this will cause also
activation of g-proteins as well as formation of a second
messenger or intracellular ligand
st
1 condition: DUAL INNERVATION of SAME structure; SAME organ
of sympathetic and parasympathetic NS = OPPOSITE EFFECTS

Example: HEART
SA NODE (automatic cell in the heart: primary pacemaker in the
heart that determines heart rate). It is innervated by a
sympathetic nerve that originate from T3, T4 AND T5 so
sympathetic preganglionic fiber will first synapse with stellate
ganglion of the sympathetic chain. Postganglionic fiber from
stellate ganglion will release Norepinephrine binding to Beta1
receptor to the heart and causes an cAMP= Ca conductance
=  heart rate
SA node can also be innervated by a parasympathetic nerve
that originate from vagus nerve of the medulla that releases
ACETYLCHOLINE binding to M2 receptor of heart causing
cAMP= K conductance= Heart rate
SAME STRUCTURE: SA node
SAME ORGAN: heart
OPPOSITE
EFFECTS
OF
SYMPATHETIC
AND
PARASYMPATHETIC NERVE

Under normal conditions, sympa and para are said to be “IN
TONE” = continuously active that fires impulses simultaneously
to maintain in a balance effect so that HR neither increases or
decreases: maintenance of normal level (regulation of heart
rate at about 75 beats/min)

SYMPATHETIC TONE present in the wall of blood vessels
(smooth muscle) which has a sympathetic innervation that
causes tonic contraction or prolonging of partial contraction
which means that the diameter of the blood vessels decreases
about 50 % of its maximum but there is still lumen so when
sympathetic increases, there will be full contraction causing
VASOCONSTRICTION in contrast to VASODILATATION caused by
decreasing of sympathetic nerves which relax the blood vessel

PARASYMPATHETIC TONE – regulates ENTERIC NEURON
causing a NORMAL PERISTALSIS; no rest of smooth muscles in
the intestines. (NO PARASYMPATHETIC TONE causes an
ATONY= NO CONTRACTION)
SAMPLE EXERCISE 2:
 ADRENRGIC: beta 1 in the heart ; Alpha 1 and beta 2
in visceral smooth muscles and glands
 CHOLINERGIC: M2 in the heart; M3 and M4 in
visceral smooth muscle and glands
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Adrenergic receptor of the heart : BETA 1
Cholinergic receptor of the heart: MUSCARINIC 2
Adrenergic receptor of intestinal smooth muscle:
ALPHA 1 AND BETA 2
Cholinergic receptor of intestinal smooth muscle: M3
AND M4
Cholinergic receptor of skeletal muscle: NICOTINIC 1
Adrenergic receptor of skeletal muscle: NONE
Cholinergic receptor of salivary glands: M3 AND M4
Adrenergic receptor of salivary glands: ALPHA 1 AND
BETA 2
Cholinergic receptor of sweat glands: M3 AND M4
Adrenergic receptor of sweat glands: NONE
Cholinergic receptor of blood vessel in skeletal muscle:
M3 AND M4
Adrenergic receptor of blood vessel in skeletal muscle:
NONE
Viscera in skin: SYMPATHETIC ADRENERGIC so it’s
either ALPHA OR BETA 2
Viscera in skin: NO CHOLINERGIC RECEPTOR
STEP 4: DEACTIVATION OF NOREPINEPHRINE
ND

Main Mechanism: REUPTAKE by SYMPATHETIC ADRENERGIC
PREGANGLIONIC FIBER Destroyed secondarily by the enzyme
MONO-AMINE OXIDASE

Another mechanism is diffusion away from the synapse For
NEP as well as circulating EPI, it is transported to the liver and
destroyed secondarily by the enzyme CATECHOL-O-METHYL
TRANSFERASE
PHYSIOLOGIC / FUNCTIONAL DIFFERENCES
 DUAL INNERVATIONS of sympathetic NS and parasympathetic
NS in ONE ORGAN: almost always have opposite effects
Page 11 of 15
2 condition: DUAL INNERVATION of DIFFERENT STRUCTURE;
SAME ORGAN = OPPOSITE EFFECTS
 Two types of smooth muscles in IRIS (colored portion of the
eye):
a.
Radial Muscle
 Innervated by a sympathetic nerve originating from
T1 AND T2
 Sympathetic preganglionic fiber will synapse with
superior cervical ganglion that will release NE and
bind to alpha 1 receptor in the radial muscle of the
iris
b.
Sphincter or Constrictor Muscle
 PARASYMPATHETIC nerve originating from
OCCULOMOTOR NERVE from the midbrain
 NTA: ACETYLCHOLINE
 Receptor: M5
C3

In the absence of light, SYMPATHETIC NS PREDOMINATES
That will cause radial muscles to contract and increases
pupillary size= PUPILLARY DILATATION/MIDRIASIS

In the presence of light, PARASYMPATHETIC NS
PREDOMINATES that cause sphincter muscle to contract and
decreases pupillary size= PUPILLARY CONSTRICTION/ MYOSIS

OPPOSITE EFFECTS
CONTRACTION)
BUT
BOTH
EXCITATORY
LONG IN DURATION
 Because of circulating EPI and
NEP from the adrenal medulla
that will reinforce sympaadrenergic affects; unlike Ach,
NEP is not immediately
deactivated by the enzyme
present in the synaptic cleft
because it’s main mechanism is
re-uptake by the pre-junctional
fiber
Fight or flight response
(CATABOLIC)
(BOTH
 Heart rate and
BP
RD
3 condition: DUAL INNERVATION of SAME structure; SAME organ
= SYNERGISTIC EFFECTS
 SALIVARY GLANDS
SYMPATHETIC stimulation will cause a mild to moderate
increase in salivary secretion
PARASYMPATHETIC stimulation will cause a profuse increase in
salivary secretion

MALE GENITALS
PARASYMPATHETIC stimulation will cause penile erection
SYMPATHETIC stimulation will cause ejaculation
Epinephrine
TH
Page 12 of 15
Peripheral
Vasoconstriction
Alpha1
Lipid breakdown
B2B3
Coronary
dilatation and
bronchial
dilatation
B2
glycogen
glucose
Sympathetic innervation:
KIDNEYS
ADRENAL MEDULLA
SWEAT GLANDS
VASCULAR SMOOTH MUSCLES
IF BLOOD VESSEL IN SKELETAL (CHOLINERGIC)
IF BLOOD VESSEL IN SKIN AND VISCERA (ADRENERGIC)
PYRO-ERECTOR MUSCLES IN THE SKIN
FUNCTIONAL DIFFERENCES
SYMPATHETIC
PARASYMPATHETIC
Enable an individual to withstand Try to conserve or preserve the
stressful or emergency conditions/ body’s processes/ “rest-or“fight-or flight” conditions
digest” response
Examples:
Examples:
Tachycardia (increase Heart rate Decrease Heart rate and Blood
and BP – beta 1 receptors)
Pressure (M2 and M3 receptor)
Peripheral vasoconstriction
Peripheral vasodilatation (M3
Increase sweating
receptor)
Palpitation
Decrease
Lipolysis
and
Lypolysis/ glycogenolysis (more Glycogenolysis, Lipogenesis ,
sources of energy- beta 2 receptor)
and bronchoconstriction (M3
Pupillary dilatation
receptors)
Bronchodilatation – beta2 receptor
Much expenditure of energy
Restore body’s processes
CATABOLIC
ANABOLIC
Beta1
Norepinephrine
4 condition: SINGLE INNERVATION
 LACRIMAL AND NASAL GLANDS that receive parasympathetic
innervation CN7 TO SPHENOPALATINE GANGLION

SHORT IN DURATION
 Because Ach is immediately
deactivated
by
Acetylcholinesterase
present in NEJ
B2&A1
Rest or Digest response
(ANABOLIC)
 Heart rate and
BP
Muscarinic and
Nicotinic
receptors
M2
Peripheral
Vasodilatation
Lipid
breakdown
Acetylcholine
(cholinergic)
Bronchial
constriction
M3
glycogen
glucose
M3
SYMPATHETIC
More generalized/ diffuse/
widespread
Reasons:
1. Extensive branching of
pre-ganglionic fiber
2. Circulating EPI and
NorEPi from adrenal
medulla
that
will
reinforce
SymAdre
effects
Reflexes are well-coordinated
Always occur at the same time
PARASYMPATHETIC
More localized (EXCEPT for
VAGUS NERVE)
Reason:
Limited branching of preganglionic fiber
PHARMACOLOGICAL DIFFERENCES
I.
CHOLINERGIC DRUGS
1.
PARASYMPATHOMIMETIC DRUGS
 Drugs that will increase or potentiate cholinergic or
parasympathetic effects
 Mimic cholinergic parasympathetic effects
 Mechanism of action:
 Increase the synthesis of Ach
 Increase the release of Ach
 Promote the interaction between Ach and
cholinergic receptors
 Decrease the inactivation of Ach
 Examples:
PILOCARPINE which functions just like Ach
stimulating muscarinic receptors
NEOSTIGMINE similar to organophosphates present
in nerve gases and pesticides that inhibits
acetylcholinesterase so there will be a decrease in
deactivation of Ach prolonging cholinergic or
parasympathetic effects
 Low doses of nicotine will transmit impulses from pre
to post = Parasympathetic effect
2.
PARASYMPATHOLYTIC DRUGS
 Drugs that will decrease or inhibit cholinergic or
parasympathetic effects
 Mechanism of action:
 Decrease/ inhibit synthesis of Ach
 Block release of Ach
 Block interaction between Ach and cholinergic
receptors
 Increase inactivation of Ach
 Antagonist of parasympathetic effects
 High doses of nicotine = BLOCKER because of
continuous depolarization causing longer refractory
period
 Examples:
BOTULINUM TOXIN or BOTOX that inhibits or blocks
the release of Ach
CURARE by blocking the binding of Ach to nicotinic
receptors to NMJ
ATROPINE that blocks Ach binding to muscarinic
receptors at NEJ
Most
Reflexes
are
well
coordinated but there are some
that does not Occur at the same
time
 Erection
 Micturition
 Defecation
Autonomic Nervous System
 Involuntary
 Activities are not mediated by the cerebral cortex
 Main autonomic center is HYPOTHALAMUS but can receive
inputs from other parts of brain like cerebral cortex
 some autonomic activities are mostly involuntary, but partly
voluntary (controlled by cerebral cortex)
O RESPIRATION
O MICTURUTION
O DEFECATION
Hypothalamus
 No specific area which can be called as autonomic center:
Anterior –regulates CHOLINERGIC / PSNS activities
Postero-Lateral –regulates ADRENERGIC/ SNS activities
 Not only regulates autonomics but also integrate somatic
endocrine autonomic activities (TEMPERATURE REGULATION)
 THERE IS VERY LITTLE EVIDENCE THAT LOCALIZED AUTONOMIC
CENTER EXISTS
Example of how ANS regulates visceral functions:
BARORECEPTOR REFLEX that regulates arterial BP
Stimulus: Increase Arterial Blood Pressure  stretch arterial walls
present in arterial wall are TWO types of BARORECEPTORS (carotid
sinus and aortic sinus) 
generate sensory impulses
transmission of afferent nerve to Cranial Nerve 9 and 10 (Sensory
division)  impulses to vasomotor center located in the medulla
decrease sympathetic outflow and increase parasympathetic
outflow (Efferent nerve)  If sympathetic, there will be a
vasodilatation and decrease heart activity; on the other hand if
parasympathetic, decrease only in heart activity Decrease Arterial
Blood Pressure (back to normal not hypotension)
Reverse is true if Decrease in BP- no stretcting of arterial wall no
impulse increase sympa; decrease para increase BP back to
normal
Page 13 of 15
II.
ADRENERGIC DRUGS
1.
SYMPATHOMIMETIC DRUGS
 Drugs that increase or potentiate sympathetic/
adrenergic effects
 Mechanism of action:
 Increase the synthesis of Norepinephrine
 Increase the release of Norepinephrine



2.
Increase the interaction between NEP and
adrenergic receptors
 Decrease the inactivation of NEP
MIMIC sympathetic adrenergic effects
Examples:
ADRENALINE (Epinephrine)
EPNEDRINE and AMPHETAMINE that increases the
release of NEP
ISOPROTERINOL a cardiac drug that stimulate beta1
receptor
SALBUTANOL that stimulate beta 2 receptors
SYMPATHOLYTIC DRUGS
 Drugs that inhibit/ decreases/ block sympathetic/
adrenergic effects
 Mechanism of action:
 Decreases the synthesis of Norepinephrine
 Block the release of Norepinephrine
 Block the interaction between NEP and
adrenergic receptors
 Increase the inactivation of NEP
 Examples:
ALPHA-BLOCKERS
BETA-BLOCKERS
CALCIUM BLOCKERS
Questions:
1. Drug given to patients with diarrhea (increase intestinal
motility-Parasympathetic): PARASYMPATHOLYTIC DRUG
(anti-cholinergic)
2. Drug given to dilate the pupil aside from Adrenaline
which is Sympathomimetic: ATROPINE (because
parasympathetic effect is constriction that competes at
Muscarinic receptor)
3. What will be the effect of a drug that decreases the
activity of acetylcholinesterase on heart rate? INCREASE
ACTIVITY OF HEART
4. What will be the effect of giving a Para sympathomimetic
drug to bronchial diameter? CONSTRICTION
5. Drug given to patients with acute asthma attack:
SYMPATHOMIMETIC
6. Drug that increases the activity of MAO: SYMPATHOLYTIC
7. Effect of drug that increases the re-uptake of NEP on
heart rate: DECREASE HEART RATE
Page 14 of 15
TABLES FROM GUYTON AND BERNE & LEVY
“Henujagon jaelza lua vala mire Henujagon kostas.”
- Any man who wishes to leave may leave.
Page 15 of 15