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 CNSs 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)
Motor Nerves (from the brain)

Carry messages from Carry orders from CNS receptors in the skin, to muscles, glands to muscles, and other contract and produce internal and external chemical messengers sense organs to the spinal cord and then to the brain

 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 Autonomic NS

Consists of nerves connected to sensory receptors and skeletal muscles Permits voluntary action (writing your name)

Permits the Involuntary functions of blood vessels, Glands and internal organs e.g.:the bladder stomach heart

Characteristic Effectors General functions

Somatic nervous system Voluntary muscle

Autonomic N. system Cardiac muscle glands, s. muscle

Adjustment to Adjustment within external environment internal environment 2 Chain ganglia, collateral ganglia or terminal ganglia Acetylcholine, adrenaline, noradrenaline

Numbers of neurons 1 Ganglia outside the CNS Neurotransmitter ------------

acetylcholine

Center

Anterior Horn cells

Lateral Horn cells

Comparison of Autonomic and Somatic Motor Systems

Autonomic nervous system
Chain of two motor neurons
Preganglionic neuron Postganglionic neuron

Conduction is slower due to thinly or unmyelinated axons

Pre-ganglionic

Post-ganglionic

Ganglion

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 Enables the body to conserve and store energy

Mobilized the body for action

Preganglionic: short, synapse Preganglionic: long, synapse within the lateral & collateral within the terminal ganglia ganglia
Postganglionic: long Postganglionic: short

Has a wide distributions

Has a restricted distributions

 Often work in opposition Cooperate to finetune homeostasis Regulated by the brain; hypothalamus, pons and medulla

Autonomic Nervous System

Can also be regulated by spinal reflexes; no higher order input Pathways both consist of a two neuron system
Preganglionic neuron from CNS autonomic ganglion outside CNS postganglionic neuron target

sympathetic division of nervous system Heart rate, blood pressure, and respiration increase Adrenal medulla secretes epinephrine and norepinephrine

HypothalamusArt) activates Fig. 45.34(TE

Blood flow to Stomach skeletal muscles contractions increases are inhibited

Sympathetic
Fight or Flight, Dealing with stress, thoracolumber, intermediolateral column, T1 -L2

Parasympathetic Rest and Digest, Vegging

Craniosacral 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 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 a or b 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 Sympathetic and Parasympathetic Divisions

Anatomical Differences in Sympathetic and Parasympathetic Divisions

Similarities between Sympathetic & Parasympathetic Both are efferent (motor) systems: visceromotor

Both involve regulation of the internal environment generally outside of our conscious control: autonomous Both involve 2 neurons that synapse in a peripheral ganglion and Innervate glands, smooth muscle, cardiac muscle
glands
CNS ganglion smooth muscle preganglionic neuron postganglionic neuron cardiac muscle

Differences between Sympathetic & Parasympathetic Location of Preganglionic Cell Bodies

Sympathetic

Parasympathetic

Thoracolumbar
T1 L2/L3 levels of the spinal cord

Craniosacral
Brain: CN III, VII, IX, X Spinal cord: S2 S4

Differences between Sympathetic & Parasympathetic Sympathetic

CNS

Relative Lengths of Neurons

ganglion target

short preganglionic neuron

long postganglionic neuron

Parasympathetic
CNS ganglion

target

long preganglionic neuron

short postganglionic neuron

Overview of the Autonomic Nervous System

Differences between Sympathetic & Parasympathetic Neurotransmitters NE (ACh at sweat glands), Sympathetic
ACh, + + / -, & receptors

All preganglionics release acetylcholine (ACh) & are excitatory (+) Symp. postgangl. norepinephrine (NE) & are excitatory (+) or inhibitory (-) Excitation or inhibition is a receptor-dependent & receptor-mediated response

Parasympathetic

ACh, +

ACh, + / muscarinic receptors

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

Overview of the Autonomic Nervous System

Differences between Sympathetic & Parasympathetic Target Tissues Sympathetic Parasympathetic Organs of head, neck, Organs of head, neck, trunk, & external genitalia trunk, & external genitalia Adrenal medulla Sweat glands in skin Arrector muscles of hair ALL vascular smooth muscle Sympathetic system is distributed to essentially all tissues (because of vascular smooth muscle) Parasympathetic system never reaches limbs or body wall (except for external genitalia)

Overview of ANS
Functional Differences
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 The somatic reflex arc arc Origin Efferent Lateral horn cells Relay in autonomic ganglia outside the CNS. -----------------------Anterior horn cells Supply the effector organ directly. present

Inter neuron Effector organs

Smooth , cardiac muscles

skeletal

Visceral Reflex Arc

Autonomic motor reflex

Interneuron

Dorsal root Fig. 45.32(TE Art) ganglion

Preganglionic neuron Postganglionic neuron Autonomic ganglion Sensory neuron

Spinal cord

Viscera

Autonomic and Somatic Motor Systems

Structure of spinal nerves: Somatic pathways

dorsal root dorsal horn dorsal root ganglion spinal nerve

dorsal ramus

CNS interneuron
ventral horn

somatic sensory nerve

(GSA)

ventral somatic ramus motor

nerve
ventral root

gray ramus communicans

sympathetic ganglion

(GSE)
white ramus communicans

Mixed Spinal Nerve

Structure of spinal nerves: Sympathetic pathways

intermediolateral gray column

dorsal ramus
spinal nerve

ventral ramus

gray ramus communicans

sympathetic ganglion

white ramus communicans

Sympathetic Division of the ANS

Sympathetic System: Preganglionic Cell Bodies

Preganglionic cell bodies in intermediolateral gray T1 L2/L3 Somatotopic organization
somatic tissues (body wall, limbs) visceral tissues (organs)

intermediolateral gray columns

T1 L2/L3

lateral horn

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

Sympathetic System: Postganglionic Cell Bodies

1. Paravertebral ganglia
Located along sides of vertebrae United by preganglionics into Sympathetic Trunk Preganglionic neurons are thoracolumbar (T1L2/L3) but postganglionic neurons are cervical to coccyx Some preganglionics ascend or descend in trunk Paravertebral ganglia

sympathetic trunk (chain)

synapse at same level

celiac ganglion sup. mesent. g. inf. mesent. g. ascend to synapse at higher level descend to synapse at lower level

Prevertebral ganglia

aorta

Sympathetic System: Postganglionic Cell Bodies

2. Prevertebral (preaortic) ganglia
Located anterior to abdominal aorta, in plexuses surrounding its major branches Preganglionics reach prevertebral ganglia via abdominopelvic splanchnic nerves Paravertebral ganglia

sympathetic trunk (chain)

abdominopelvic splanchnic nerve

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

Prevertebral ganglia

aorta

Sympathetic Trunk Ganglia

Sympathetic System: Summary

visceral tissues
(organs)

1- Cervical division 4- somatic tissues

(body wall, limbs)
T1

2- Cardiopulmonary Splanchnics: postganglionic fibers to thoracic viscera

postganglionics via 31 spinal nerves to somatic tissues of neck, body wall, and limbs sympathetic trunk
L2

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

prevertebral ganglia

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

Face skin blood vessel: Vasoconstriction of (Pale color). Sweet secretion: copious secretion. Hair: erection due to contraction of erector pilae muscles.. Cerebral vessels: Weak vasoconstriction

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 division

Origin: Preganglionic nerve fibers arise from all lateral horn cells of all sympathetic segments, and then relay in the cervical and sympathetic chain ganglia. Course: Postganglionic nerve fibers emerge from these ganglia proceeds outside the central nervous system to return back to spinal cord to join the spinal nerve when it comes out from the anterior horn cells, and supply the following structures: Skin:
Vasoconstriction giving the pale color of the skin. Stimulation of the sweet glands, the eccrine glands give copious secretion, while the apocrine glands give thick odoriferous secretion. Hair erection.

Skeletal muscle:
Its blood vessels show vasodilatation (V.D.) due to cholinergic effect or vasoconstriction (V.C.) due to a adrenergic effect. The type of stimulation depends upon the nature of stimulation. Muscles: its stimulation causing delayed fatigue and early recovery.

4- somatic tissues (body wall, limbs)

postganglionics via 31 spinal nerves to somatic tissues of neck, body wall, and limbs

sympathetic trunk

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

Parasympathetic Pathways
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
S2S4 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 IXII 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 Nerve

Origin: Edinger-Westphal nucleus at midbrain. Course: preganglionic from E-W nucleus to rely in the ciliary ganglion. Postganglionic supply: 1- pupillconstrictor muscle 2- ciliary muscle. 3- four of the extrinsic eye muscles. Its stimulation leads to miosis, accommodation to neat vision and movements of the eye ball.

CN III: Oculomotor Nerve

Innervates four of the extrinsic eye muscles

CN VII: Facial Nerve

Origin: The superior salivary nucleus which is a part of facial nucleus in the lower part of pons. Course: Preganglionic nerve fibers run in the chorda tympani nerve which is a part of facial nerve and relay in:- Submaxillary ganglion - Sphenopalatine ganglion. Postganglionic nerve arises from Submaxillary ganglion supply submandibular and sublingual salivary glands and anterior 2/3 of the tongue. Postganglionic nerve arises from Sphenopalatine ganglion supply the mucosa of the soft palate and nasopharynx and Lacrimal glands. Its stimulation causes vasodilatation and secretion at their effector organs.

CN VII: Facial Nerve

Innervates muscles of facial expression Sensory innervation of face Taste

CN IX: Glossopharyngeal Nerve

Origin: Glossopharyngeal nerve nucleus in the upper part of the medulla oblongata called inferior salivary nucleus, and then relay in the otic ganglion. Course: Postganglionic nerve fibers arise from otic ganglion supply the parotid salivary gland and posterior 1/3 of the tongue Its stimulation causes vasodilatation and secretion at their effector organs

CN IX: Glossopharyngeal Nerve

Sensory and motor innervation of structures of the tongue and pharynx Taste

CN X: Vagus Nerve
Origin: Dorsal vagus nucleus in medulla oblongata Course: Postganglionic nerve fibers from the terminal ganglia which supplied from dorsal vagus nucleus and supply the following structures: HEART: The vagus nerve supplies the both auricles and don't supply the ventricles (and this called vagus escape 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 Outflow
Origin: Preganglionic nerve fibers arise from the lateral horn cells of the 2nd, 3rd and 4th sacral segments. Course: These preganglionic passes without relay, then the right and left branches unit together to form the pelvic nerve, the pelvic nerve relay in the terminal ganglia, where the postganglionic nerve fibers emerge and supply the following structures:Urinary bladder: parasympathetic stimulation causes: - Contraction of the bladder wall - Relaxation of its sphincter. - These responses lead to micturition.

Rectum and descending colon: parasympathetic stimulation causes: - Contraction of its wall. - Relaxation of internal anal sphincter. - These responses lead to defecation. Seminal vesicles and prostate: parasympathetic stimulation -causes: - Secretion of these glands. Erectile tissue: parasympathetic stimulation causes: - Vasodilatation which lead to erection.

Chemical transmission
The traveling of signal in the nervous system between different neurons is mediated by the effect of a chemical substance released at the nerve terminal called chemical transmitter. In the sympathetic nervous system the chemical transmitter is adrenaline, noradrenaline or sometimes acetylcholine. When the chemical transmitter is adrenaline the nerve fiber is called adrenergic, but when the chemical transmitter is acetylcholine, the nerve fiber is called cholinergic.

Nerves Contact Other Cells at Synapses

The synapse is the relay point where information is conveyed from neuron to neuron by chemical transmitters. At a synapse the axon usually enlarges to from a button ' which is the information delivering part of the junction. The terminal button contains tiny spherical structures called synaptic vesicles, each of which can hold several thousand molecules of chemical transmitter. On the arrival of a nerve impulse at the terminal button, some the vesicles discharge their contents into the narrow cleft that separates the membrane of another cell's dendrite, which is designated to receive the chemical message.

 Chemical transmitters carry the signal across 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 recycledit 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 sites

1-Preganglionic nerve fibres of both sympathetic and parasympathetic divisions of the autonomic nervous system. 2-Postganglionic nerves of the parasympathetic division. 3- The sympathetic innervation of sweet glands. 4- Neuromuscular junction. 5- Autonomic ganglion to the adrenal gland.

Neurotransmitter release sites

Acetylcholine inactivation

In

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

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

Acetylcholine receptors
Acetylcholine effects on the tissue are the result of its action on the receptor present in the membrane of the effector 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 receptors
Nicotinic receptors (Central) Types Two types:Ganglionic Neruomuscular Nicotine in small doses, Ach, metacholine Muscarinic receptors (peripheral ) M1, M2 (cardiac), M3 (glandular&smooth muscle) M4 (brain).M5,M6 and M7. Muscarine, Ach, carbarcholine

Stimulated by Blocked by

Nicoitin in large doses- Atropine decameyhonium scopolamine d-tubourarineAutonomic ganglia M.E.P Adrenal medulla Preganglionic neuron. Parasympathetic (pre-postganglionic) Sympathetic postganglionic nerve endings (sweat glands & skeletal muscle).

site

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

Primary Neurotransmitter Receptors & Second Messenger Systems

norepinephrine epinephrine (~20%) Adrenergic GPCRs a1 IP3/DAG, [Ca2+]i PKC a2 - cAMP/PKA b1 - cAMP/PKA b2 - cAMP/PKA b3 - cAMP/PKA Adrenal Medulla (epi:norepi::80:20)

acetylcholine

Muscarinic GPCRs M1 IP3/DAG, [Ca2+]i PKC M2 cAMP/PKA, PI(3)K M3 cAMP/PKA, IP3/DAG, [Ca2+]i PKC M4 M5 IP3/DAG, [Ca2+]i PKC

Comparison of sympathetic and Parasympathetic Pathways

Neurotransmitters Receptors

Drugs Affecting the Autonomic Nervous System

Parasympathomimetic drugs: These are drugs which exert an action similar to acetylcholine and there are two types:- Drugs directly stimulate cholinergic receptors - Drugs inhibit cholinesterase enzyme. Parasympatholytic Drugs: These drugs antagonize the action of acetylcholine.

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

Parasympathomimetic drugs
These are drugs which exert an action similar to the action of acetylcholine and it is divided into two groups: (A) Drugs that directly stimulate the cholinergic receptors: These include Ach derivatives that not hydrolyzed rapidly by cholinesterase e.g. metacholine, carbachol, poiolocarpine and muscarine. (B) Drugs that inhibit the cholinesterase enzyme: These drugs preserve the action of Ach by preventing the action of cholinesterase enzyme and they are two types:(1) Drugs which has a reversible effect i.e. their action is temporary e.g. eserine (phyostigmine) and prostigmine (neostigmine).
- Eserine: is a generalized drugs which causes generalized blocking allover the body, thus we use it locally as an eye drops in treatment of glaucoma otherwise it will cause generalized parasympathetic effect. - Neostigmine:It was used in treatment of myasthenia gravis due to its direct action on the motor end plate.

(2) Drugs which have irreversible effect i.e. their action are prolonged e.g. parathion (an insecticide) and D.F.P. (Diisopropyflurophosphate), which is a toxic nerve gas.

Parasympatholytic Drugs
These drugs which antagonize the action of Ach by one of the following mechanisms: Competitive inhibition: These drugs occupy the Ach receptors and present its action. Persistent depolarization: These drugs cause prolonged depolarization of Ach receptor thus they prevent the excitation of the receptor by the released Ach.

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

e.g.AtropineHomatropine Hyoscine

e.g. -Nicotine in large doses. - Arfonad - Hexamethonium

Competitive inhibition. -Persistent depolarization

e.g. - curare

Mechanism of actioncompetitive inhibition Clinical use: Atropine used for:-dilation of pupil- relive spasm- prevent bronchial secretion

Competitive inhibition.

- Ganglion blocker used - Curare is used as a for blocking conduction in muscle relaxant sympathetic ganglion of hypertension.

Sympathetic (Adrenergic) Drugs

NADP+
from phe, diet, or protein breakdown

NADPH DHBR

BH4 Tyrosine 1

BH2 L-Dopa Tyrosine hydroxylase 2

(rate-determining step) H O 2

O2
DPN OHase in neuroscretory granules

H2O

3 ascorbate

O2

CO2

Dopa decarboxylase pyridoxal phosphate

Norepinephrine Dopamine hydroxylase PNMT Epinephrine 4 SAM SAH

PNMT specific to adrenal medulla

Dopamine
Parkinsons disease: local deficiency of dopamine synthesis; L-dopa boosts production

SAM from metabolism of Met

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

dihydrobiopterin reductase; PNMT, phenylethanolamine N-CH3 transferase; SAH, Sadenosylhomocysteine; SAM, S-adenosylmethionine

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

Stress Chronic regulation Hypothalamus ACTH Cortisol Tyrosine

from adrenal cortex via intraadrenal portal system

Acute regulation

L-Dopa

DPN induction

granule
Neuron

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

Ca2+

DPN NE

PNMT
NE promotes exocytosis E

Epinephrine

acetylcholine Adrenal Medulla Chromaffin Cell

E E E NE E

EEE NE

E E NE EE

neurosecretory granules

Epinephrine Norepinephrine

COMT + MAO Vanillylmandelic acid

COMT + MAO

Dopamine

Homovanillic acid

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

Degradation of epinephrine, norepinephrine and dopamine via monoamine oxidase (MAO) and catechol-O-methyl-transferase (COMT)

Table 1. Classification of Adrenergic Hormone Receptors

Receptor alpha1 (a1) alpha2 (a2) beta1 (b1) beta2 (b2) Agonists E>NE NE>E E=NE E>>NE Second Messenger IP3/Ca2+; DAG cyclic AMP cyclic AMP cyclic AMP G protein Gq Gi Gs Gs

E = epinephrine; NE = norepinephrine Synthetic agonists: isoproterenol binds to beta receptors phenylephrine binds to alpha receptors (nose spray action) Synthetic antagonists: propranolol binds to beta receptors phentolamine binds to alpha receptors

NH2

HOOC

Figure 4. Model for the structure of the b2-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) a1-receptor Process (IP3, DAG) Carbohydrat liver e glycogenolysis metabolism a2receptor b 1receptor b2-receptor ( cAMP) liver/muscle glycogenolysis; liver gluconeogenesis; glycogenesis No effect insulin and glucagon secretion Smooth muscle relaxation - bronchi, blood vessels, GI tract, genitourinary tract

( cAMP)
No effect

( cAMP)
No effect

Fat metabolism
Hormone secretion

No effect No effect Smooth muscle - blood vessels, genitourinary tract

lipolysis insulin secretion Smooth muscle some vascular; GI tract relaxation

lipolysis No effect

Muscle contraction

Myocardial - rate, force

b1 or b2 receptor

a2 receptor

Gs

Gi

as b

GTP GTP

ai ai
GTP GTP

as

inactive adenylyl cyclase ATP

ACTIVE adenylyl cyclase

inactive adenylyl cyclase

cyclic AMP

Figure 5. Mechanisms of b1, b2, and a2 agonist effects on adenylyl cyclase activity

"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.

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

epinephrine

[1] dissociation

[2]

a GTP AC

a GDP

[5] GTPase [6]

OH OH

[3]

[4]

degradation to VMA

ATP cAMP AMP phosphodiesterase

activated PKA phosphorylates enzymes

OP OP phosphorylation of b-receptor by b-ARK decreases activity even with bound hormone

OPOP binding of b-arrestin further inactivates receptor despite bound hormone

OH [7]

OP

insulin activation of protein phosphatase to dephosphorylate enzymes

B1 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 A1 receptors are found most commonly in sympathetic target tissues A2 receptors are found in the GI tract and pancreas (relaxation)