autonomic nervous system Ppt

AUTONOMIC NERVOUS SYSTEM

BY

Dr. Lawrence A. Olatunji Lecturer,

Physiology Department

Central nervous system

• The nervous system with the endocrine system controls and coordinates various functions of the body.

• 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 can be classified:

• Anatomically, according to its different structures,

• Physiologically, according to its functions.

Anatomically nervous system formed of (Somatic nervous system, autonomic nervous system and integrative nervous system).

Peripheral Nervous System• Handles the CNS’s input and output.

• Contains all the portions of the NS outside the brain and spinal cord.

• Contains sensory nerves and motor nerves

• Divided into autonomic nervous system and somatic nervous

system.

Peripheral Nervous System• Sensory Nerves

(to the brain)

Carry messages from receptors in the skin,

muscles, and other 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 to contract and produce

chemical messengers

• The ANS is part of the peripheral nervous system and it controls many organs and

muscles within the body.

• In most situations, we are unaware of the workings of the ANS because it functions in

an involuntary, reflexive manner.

• For example, we do not notice when blood vessels change size or when our heart beats

faster.

• However, some people can be trained to control some functions of the ANS such as

heart rate or blood pressure.

The ANS is most important in two situations:

1- In emergencies that cause stress and require us to "fight" or take

"flight" (run away).

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

• It is usual to divide the nervous system into somatic, autonomic and

integrated systems.

• The somatic nervous system provides voluntary motor control of skeletal

muscle.

• The autonomic nervous system provides an involuntary control of

internal environment and the viscera.

• The two systems are anatomically separated form each other, but functionally

they cannot perform their work independently, and

they work with each other in an integrated manner

Peripheral Nervous System• Somatic NS

Consists of nerves connected to sensory receptors and skeletal muscles

Permits voluntary action (writing your name)

• Autonomic NS

Permits theInvoluntary functions

of blood vessels,Glands and

internal organs e.g.:- the bladder stomach

heart

Characteristic Somatic nervous system

Autonomic N. system

Effectors Voluntary muscle Cardiac muscle glands, s. muscle

General functions Adjustment to external environment

Adjustment within internal environment

Numbers of neurons 1 2

Ganglia outside the CNS

------------ Chain ganglia, collateral ganglia or terminal ganglia

Neurotransmitter acetylcholine Acetylcholine, adrenaline, noradrenaline

Center Anterior Horn cells Lateral Horn cells

Comparison of Autonomic and Somatic Motor Systems

• Autonomic nervous system– Chain of two motor neurons

• Preganglionic neuron• Postganglionic neuron

– Conduction is slower due to thinly or unmyelinated axons

Pre-ganglionic

Ganglion

Post-ganglionic

Sympathetic N.S. Parasympathetic N.S.

Like the accelerator of your car

Like the brakes in your car

Slows the body down to keep its rhythm

Mobilized the body for action

Enables the body to conserve and store energy

Preganglionic: short, synapse within the lateral & collateral ganglia

Preganglionic: long, synapse within the terminal ganglia

Postganglionic: long Postganglionic: short

Has a wide distributions Has a restricted distributions

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

Fig. 45.34(TE Art)Hypothalamus activatessympathetic division ofnervous system

Heart rate, blood pressure,and respiration increase

Blood flow toskeletal musclesincreases

Stomachcontractions are inhibited

Adrenal medulla secretes epinephrine and norepinephrine

SympatheticFight or Flight, Dealing with

stress, thoracolumber, intermediolateral column, T1 -L2

ParasympatheticRest and Digest,

VeggingCraniosacral S2-S4,

Sympathetic nerve endings also activate the release of NE and E from the adrenal medulla

Enhances effects of NE from sympathetic nerve endings

Adds the effects of E to the overall arousal (“fight or flight”) pattern

The Autonomic SystemThe Autonomic System

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

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

Anatomical Differences in Sympatheticand Parasympathetic Divisions

Anatomical Differences in Sympatheticand Parasympathetic Divisions

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

preganglionicneuron

postganglionicneuron

glands

smoothmuscle

cardiacmuscle

Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic

Location of Preganglionic Cell Bodies

ThoracolumbarT1 – L2/L3 levels of the spinal cord

CraniosacralBrain: CN III, VII, IX, XSpinal cord: S2 – S4

Sympathetic Parasympathetic

SympatheticCNS ganglion

short preganglionicneuron

long postganglionicneuron

target

ParasympatheticCNS ganglion

long preganglionicneuron

target

short postganglionicneuron

Differences between Sympathetic & ParasympatheticDifferences between Sympathetic & Parasympathetic

Relative Lengths of Neurons

Parasympathetic

Overview of the Autonomic Nervous SystemOverview of the Autonomic Nervous SystemDifferences 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, +

Overview of the Autonomic Nervous SystemOverview of the Autonomic Nervous SystemDifferences 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)

Overview of ANSOverview of ANSFunctional 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

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

Visceral Reflex Arc

Fig. 45.32(TE Art)

Viscera

Autonomicganglion

Postganglionic neuron

Autonomic motor reflex

Interneuron Dorsal rootganglion

Preganglionicneuron

Sensoryneuron

Spinalcord

Autonomic and Somatic Motor Systems

Structure of spinal nerves: Somatic pathwaysStructure of spinal nerves: Somatic pathways

dorsal rootdorsal rootganglion

ventral root

spinalnerve

dorsalramus

ventralramus

dorsalhorn

ventralhorn

somaticsomaticsensorysensory

nervenerve(GSA)(GSA)

somaticsomaticmotormotornervenerve(GSE)(GSE)

CNSinter-

neuron

CNSinter-

neuron

Mixed SpinalMixed SpinalNerveNerve

Mixed SpinalMixed SpinalNerveNerve

gray ramuscommunicans white ramus

communicans

sympatheticganglion

spinalnerve

dorsalramus

ventralramus

gray ramuscommunicans white ramus

communicans

sympatheticganglion

intermediolateralgray column

Structure of spinal nerves: Sympathetic pathwaysStructure of spinal nerves: Sympathetic pathways

Sympathetic Division of the ANS

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

intermediolateralgray columns

lateralhorn

T1 –L2/L3

Clinical Relevance» dysfunction due to cord injury» spinal nerve impingement & OMM» referred pain

Sympathetic System: Postganglionic Cell BodiesSympathetic System: Postganglionic Cell Bodies

Paravertebralganglia

Prevertebral ganglia

• celiac ganglion• sup. mesent. g.• inf. mesent. g.

aorta

sympathetictrunk (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 atsame level

ascend tosynapse athigher level

descend tosynapse atlower level

Sympathetic System: Postganglionic Cell BodiesSympathetic System: Postganglionic Cell Bodies

Paravertebralganglia

Prevertebral ganglia

• celiac ganglion• sup. mesent. g.• inf. mesent. g.

aorta

sympathetictrunk (chain)

2. Prevertebral (preaortic) ganglia• Located anterior to abdominal aorta, in plexuses

surrounding its major branches• Preganglionics reach prevertebral ganglia via abdominopelvic splanchnic nerves

abdominopelvicsplanchnic

nerve

Sympathetic Trunk Ganglia

Sympathetic System: SummarySympathetic System: Summary

T1

L2

4- somatic tissues

(body wall, limbs)

visceral tissues(organs)

postganglionicsvia 31 spinal

nervesto somatic tissues of neck, body wall,

and limbs

sympathetictrunk

prevertebralganglia

2- Cardiopulmonary Splanchnics: postganglionic fibers to thoracic viscera

3- Abdominopelvic Splanchnics: preganglionic fibers to prevertebral ganglia, postganglionic fibers to abdominopelvic viscera

1- Cervical division

1- Cervical divisionOrigin: 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

Sympathetic Pathways to the Head

(2) Cardiopulmonary division

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

Course: Preganglionic neurons reach the sympathetic chain to relay in the three cervical ganglion and upper four thoracic

ganglion.

The postganglionic arise from these ganglia supply the following structures:-

• Heart: Increase all properties of cardiac muscle (contraction,

rhythmicity, excitability, conductivity.• Coronary vessels, its sympathetic supply. At first it

causes vasoconstriction, and then it causes vasodilatation due to accumulation of metabolites.

• Bronchi: Broncho dilation, decrease bronchial secretions and

vasoconstriction of pulmonary blood vessels.

Sympathetic Pathways to Thoracic Organs

3- Splanchnic division

Origin: lateral horn cells of the lower six thoracic and upper four lumber segments.Course: Preganglionic neurons originate from these segments reach the sympathetic

chain where they pass without relay, and then they divided into two branches:(1) Greater splanchnic nerve (2) Lesser splanchnic nerve.

Greater splanchnic nerve:• Origin: Preganglionic nerves fibers emerge from lateral horn cells of lower six

thoracic segments and then relay in the collateral ganglion in the abdomen.• Course: Postganglionic nerve fibers arise from these ganglia (celiac, superior

mesenteric and inferior mesenteric ganglia) and supply the abdominal organs causing the following effects:

• Vasoconstriction: of most arteries of stomach, small intestine, proximal part of large intestine, kidney, pancreas and liver.

• Relaxation of the musculature of: stomach, small intestine and proximal part of large intestine.

• Contraction of sphincters: of the stomach and intestine leading to (food retention).• Contraction of the capsule: of the spleen leading to evacuation of about 200 ml of

blood. • Breakdown of the glucose in the liver: (glycogenolysis) leading to increase of

blood glucose level.• Stimulation of adrenal medulla: Secrete adrenaline and noradrenalin.

Sympathetic Pathways to the Abdominal Organs

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.

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.

Sympathetic Pathways to the Pelvic Organs

(4) Somatic divisionOrigin: 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.

4- somatic tissues(body wall, limbs)

postganglionicsvia 31 spinal nerves

to somatic tissues of neck, body wall, and limbs

sympathetictrunk

Sympathetic Pathways to Periphery

Figure 15.9

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

The Adrenal Medulla

ParasympatheticParasympatheticPathwaysPathways

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

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

The Parasympathetic Division

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

The 12 Pairs of Cranial Nerves

CN I: Olfactory Nerves

• Sensory nerves of smell

CN II: Optic Nerve

• Sensory nerve of vision

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

CN IV: Trochlear Nerve

• Innervates an extrinsic eye muscle

CN V: Trigeminal Nerve• Provides sensory innervation to the face

– Motor innervation to chewing muscles

CN VI: Abducens Nerve

• Abducts the eyeball

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

CN VIII: Vestibulocochlear Nerve

• Sensory nerve of hearing and balance

CN IX: Glossopharyngeal Nerve• Sensory and motor innervation of structures of

the tongue and pharynx• Taste

CN X: Vagus Nerve• A mixed sensory and motor nerve

• Main parasympathetic nerve– “Wanders” into thorax and abdomen

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

neck muscles

CN XII: Hypoglossal Nerve• Runs inferior to the tongue

– Innervates the tongue muscles

Cranial Outflow

• Preganglionic fibers run via:– Oculomotor nerve (III)– Facial nerve (VII)– Glossopharyngeal nerve (IX)– Vagus nerve (X)

• Cell bodies located in cranial nerve nuclei in the brain stem

CN III: Oculomotor NerveOrigin: 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.

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

CN VII: Facial NerveOrigin: The superior salivary nucleus which is a part of

facial nucleus in the lower part of pons.Course: Preganglionic nerve fibers run in the chorda

tympani nerve which is a part of facial nerve and relay in:-

- Submaxillary ganglion- Sphenopalatine ganglion.

• Postganglionic nerve arises from Submaxillary ganglion supply submandibular and sublingual salivary glands

and anterior 2/3 of the tongue. • Postganglionic nerve arises from Sphenopalatine

ganglion supply the mucosa of the soft palate and nasopharynx and Lacrimal glands.

• Its stimulation causes vasodilatation and secretion at their effector organs.

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

CN IX: Glossopharyngeal NerveOrigin: Glossopharyngeal nerve nucleus in

the upper part of the medulla oblongata called inferior salivary nucleus, and then

relay in the otic ganglion.

Course: Postganglionic nerve fibers arise from otic ganglion supply the parotid

salivary gland and posterior 1/3 of the tongue

Its stimulation causes vasodilatation and secretion at their effector organs

CN IX: Glossopharyngeal Nerve• Sensory and motor innervation of structures of

the tongue and pharynx• Taste

CN X: Vagus NerveOrigin: 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.

• Lungs: Vagus stimulation causes:• Bronchoconstriction.• Increased bronchial secretion.• Vasodilatation of pulmonary blood vessels.• These responses lead to precipitation of asthma.

Gastrointestinal tract: Vagus stimulation causes:• Contraction of walls of esophagus, stomach, small intestine and

proximal part of large intestine.• Relaxation of their corresponding sphincter.• These responses promote deglutition, increased secretion of GIT and

evacuation of foods.

• Gall bladder: Vagus stimulation causes:• Contraction of the gall bladder wall.• Relaxation of its sphincter.• These responses lead to evacuation of the gall bladder.

CN X: Vagus Nerve

Sacral OutflowOrigin: Preganglionic nerve fibers arise from the

lateral horn cells of the 2nd, 3rd and 4th sacral segments.

Course: These preganglionic passes without relay, then the right and left branches unit together to form

the pelvic nerve, the pelvic nerve relay in the terminal ganglia, where the postganglionic nerve

fibers emerge and supply the following structures:- Urinary bladder: parasympathetic stimulation

causes:- Contraction of the bladder wall

- Relaxation of its sphincter.- These responses lead to micturition.

Rectum and descending colon:

parasympathetic stimulation causes:

- Contraction of its wall.

- Relaxation of internal anal sphincter.

- These responses lead to defecation.

Seminal vesicles and prostate:

parasympathetic stimulation -causes:

- Secretion of these glands.

Erectile tissue: parasympathetic stimulation causes:

- Vasodilatation which lead to erection.

Chemical transmissionThe traveling of signal in the nervous system between different neurons is mediated by the

effect of a chemical substance released at the nerve terminal called chemical transmitter.

In the sympathetic nervous system the chemical transmitter is adrenaline, noradrenaline or

sometimes acetylcholine.

When the chemical transmitter is adrenaline the nerve fiber is called adrenergic, but when the

chemical transmitter is acetylcholine, the nerve fiber is called cholinergic.

Nerves Contact Other Cells at Synapses• The synapse is the relay point where information is

conveyed from neuron to neuron by chemical transmitters.

• At a synapse the axon usually enlarges to from a button ' which is the information delivering part of the

junction. • The terminal button contains tiny spherical structures

called synaptic vesicles, each of which can hold several thousand molecules of chemical transmitter.

• On the arrival of a nerve impulse at the terminal button, some the vesicles discharge their contents into

the narrow cleft that separates the membrane of another cell's dendrite, which is designated to receive

the chemical message.

• Chemical transmitters carry the signal across 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

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

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.

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.

Acetylcholine release sites1-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.

Neurotransmitter release sites

Acetylcholine inactivation

In synaptic cleft, Acetylcholinesterase breaks it down into acetate and choline.

50% of choline then re up taken into presynaptic neuron.

Acetylcholine receptorsAcetylcholine 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.

Cholinergic receptorsNicotinic 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).

Nicotinic Receptors

• Located in the ganglia of both the PSNS and SNS

• Named “nicotinic” because can be stimulated by the alkaloid nicotine

Muscarinic Receptors

• Located postsynaptically:– Smooth muscle– Cardiac muscle– Glands of parasympathetic fibers– Effector organs of cholinergic sympathetic

fibers

• Named “muscarinic” because can be stimulated by the alkaloid muscarine

Parasympathetic (Cholinergic) Drugs

Subdivisions of the Autonomic Nervous System

Sympathetic Parasympathetic

PrimaryNeurotransmitter

norepinephrineepinephrine (~20%)

acetylcholine

Receptors&

SecondMessenger

Systems

Adrenergic GPCRs1 – IP3/DAG, [Ca2+]i PKC2 - cAMP/PKA

1 - cAMP/PKA2 - cAMP/PKA3 - cAMP/PKA

Muscarinic GPCRsM1 – IP3/DAG, [Ca2+]i PKCM2 – cAMP/PKA, PI(3)KM3 – cAMP/PKA, IP3/DAG, [Ca2+]i PKCM4 – M5 – IP3/DAG, [Ca2+]i PKC

Adrenal Medulla(epi:norepi::80:20)

• Neurotransmitters

• Receptors

Comparison of sympathetic and Parasympathetic Pathways

Drugs Affecting the Autonomic Nervous System

Parasympathomimetic drugs:

These are drugs which exert an action similar to acetylcholine and there are two types:-

- Drugs directly stimulate cholinergic receptors - Drugs inhibit cholinesterase enzyme.

Parasympatholytic Drugs:

These drugs antagonize the action of acetylcholine.

Cholinergic Agents• Drugs that stimulate the parasympathetic

nervous system (PSNS).

• Drugs that mimic the effects of the PSNS neurotransmitter

• Acetylcholine (ACh)

Parasympathomimetic drugsThese are drugs which exert an action similar to the action of

acetylcholine and it is divided into two groups: (A) Drugs that directly stimulate the cholinergic receptors:

These include Ach derivatives that not hydrolyzed rapidly by cholinesterase e.g. metacholine, carbachol, poiolocarpine and

muscarine. (B) Drugs that inhibit the cholinesterase enzyme: These drugs

preserve the action of Ach by preventing the action of cholinesterase enzyme and they are two types:-

(1) Drugs which has a reversible effect i.e. their action is temporary e.g. eserine (phyostigmine) and prostigmine (neostigmine).

• - Eserine: is a generalized drugs which causes generalized blocking allover the body, thus we use it locally as an eye drops in treatment of glaucoma otherwise it will cause generalized parasympathetic effect.

• - Neostigmine:It was used in treatment of myasthenia gravis due to its direct action on the motor end plate.

(2) Drugs which have irreversible effect i.e. their action are prolonged e.g. parathion (an insecticide) and D.F.P.

(Diisopropyflurophosphate), which is a toxic nerve gas.

Parasympatholytic Drugs• These drugs which antagonize the action

of Ach by one of the following mechanisms:-

• Competitive inhibition: These drugs occupy the Ach receptors and present its

action.• Persistent depolarization: These drugs

cause prolonged depolarization of Ach receptor thus they prevent the excitation of

the receptor by the released Ach.

Parasympatholytic drugsMuscarinic 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

Sympathetic (Adrenergic) Drugs

DHBR

NADP+

NADPHfrom phe, diet, or protein breakdown

Tyrosine L-Dopa

H2OO2

Tyrosine hydroxylase(rate-determining step)

BH2BH4

1

Dopadecarboxylase

CO2

Dopamine

pyridoxalphosphate

2

Dopamine hydroxylase

ascorbateH2O

Norepinephrine

O23

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

........

acetylcholine

Adrenal MedullaChromaffin Cell

Neuron

Acuteregulation

Tyrosine

L-Dopa DPN

DPN NE

granuleinduction

Chronicregulation

Stress

Hypothalamus

ACTH

Cortisolfrom adrenal cortex via intra-adrenal portal system

EpinephrinePNMT

NE

neuro-secretorygranules

E E ENE E

Regulation of the release of catecholamines and synthesis of epinephrine in the adrenal medulla chromaffin cell.

promotesexocytosis

................

EEEENE

E

E E

NE

E

Ca2+

Norepinephrine

Epinephrine COMT + MAOVanillylmandelic 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 acidCOMT + MAO

Table 1. Classification of Adrenergic Hormone Receptors

Receptor AgonistsSecond

MessengerG protein

alpha1 (1) E>NE IP3/Ca2+; DAG Gq

alpha2 (2) NE>E cyclic AMP Gi

beta1 (1) E=NE cyclic AMP Gs

beta2 (2) E>>NE cyclic AMP Gs

E = epinephrine; NE = norepinephrine

Synthetic agonists:isoproterenol binds to beta receptorsphenylephrine binds to alpha receptors (nose spray action)

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

NH2

HOOC

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

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

Process

1-receptor

(IP3, DAG)

2-receptor

( cAMP)

1-receptor

( cAMP)

2-receptor

( cAMP)

Carbohydratemetabolism

liver glycogenolysis

No effect No effect

liver/muscle glycogenolysis; liver gluconeogenesis; glycogenesis

Fatmetabolism

No effect lipolysis lipolysis No effect

Hormonesecretion

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

1 or 2

receptor

ATP cyclic AMP

Gs

s

GTP

inactiveadenylylcyclase

GTP

ACTIVEadenylylcyclase

inactiveadenylylcyclase

2 receptor

Figure 5. Mechanisms of 1, 2, and 2 agonist effects on adenylyl cyclase activity

Gi

i

GTPs

GTP

i

X

"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 glycogenolysismobilizes glucose for the brain by hepatic glycogenolysis/

gluconeogenesispreserves 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.

OH OP

[2]

degradation to VMA

insulin activation of protein phosphatase to dephosphorylate enzymes[7]

[5]

GTPase

GDP

epinephrine

phosphorylationof -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 PKAphosphorylatesenzymes

[6]AMP

phosphodiesterase

GTP

[1]dissociation

Figure 6. Mechanisms for terminating the signal generated by epinephrine binding to a -adrenergic receptor

1 found on heart muscle and in certain cells of the kidney

B2 found in certain blood vessels, smooth muscle of airways; found where sympathetic neurons ARE NOT

1 receptors are found most commonly in sympathetic target tissues

A2 receptors are found in the GI tract and pancreas (relaxation)