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Peripheral Nervous System
the CNS¶s input and output. y Contains all the portions of the NS outside the brain and spinal cord. y Contains sensory nerves and motor nerves y 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 sense organs to the messengers 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. y In most situations, we are unaware of the workings of the ANS because it functions in an involuntary, reflexive manner. y For example, we do not notice when blood vessels change size or when our heart beats faster. y 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".
is usual to divide the nervous system into somatic, autonomic and integrated systems. y The somatic nervous system provides voluntary motor control of skeletal muscle. y The autonomic nervous system provides an involuntary control of internal environment and the viscera.
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
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 Lateral Horn cells
Numbers of neurons 1 Ganglia outside the -----------CNS Neurotransmitter acetylcholine
Anterior Horn cells
Comparison of Autonomic and Somatic Motor Systems
Autonomic nervous system
Chain of two motor neurons
x Preganglionic neuron x Postganglionic neuron
Conduction is slower due to thinly or unmyelinated axons
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
Preganglionic: long, synapse within the terminal ganglia Postganglionic: short Has a restricted distributions
Mobilized the body for action
Preganglionic: short, synapse within the lateral & collateral ganglia Postganglionic: long Has a wide distributions
Often work in opposition Cooperate to finetune 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 from CNS
Autonomic Nervous System
autonomic ganglion outside CNS
Hypothalamus activates Fig. 45.34(TE Art) sympathetic division of nervous system Heart rate, blood pressure, and respiration increase Adrenal medulla secretes epinephrine and norepinephrine
Stomach Blood flow to skeletal muscles contractions are inhibited increases
Fight or Flight, Dealing with stress, thoracolumber, intermediolateral column, T1 -L2
Parasympathetic Rest and Digest,
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 (³fight or flight´) pattern
The Autonomic System
Sometimes called the ³thoracolumbar´ 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 E or F receptors Target tissues are smooth muscle, cardiac muscle, endocrine glands, brown fat
Sometimes called the ³cranio-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: ³visceromotor´
Both involve regulation of the ³internal´ environment generally outside of our conscious control: ³autonomous´ 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
T1 ± L2/L3 levels of the spinal cord
Brain: CN III, VII, IX, X Spinal cord: S2 ± S4
Differences between Sympathetic & Parasympathetic Sympathetic
Relative Lengths of Neurons
short preganglionic neuron
long postganglionic neuron
long preganglionic neuron
short postganglionic neuron
Overview of the Autonomic Nervous System
Differences between Sympathetic & Parasympathetic Neurotransmitters NE (ACh at sweat glands), Sympathetic
ACh, + + / -, & ß receptors
All preganglionics release acetylcholine (ACh) & are excitatory (+) Symp. postgangl. ² norepinephrine (NE) & are excitatory (+) or inhibitory (-) Excitation or inhibition is a receptor-dependent & receptor-mediated response
ACh, + / muscarinic receptors
Parasymp. postgangl. ² 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
³Fight or flight´ Catabolic (expend energy)
³Feed & breed´, ³rest & digest´ Homeostasis
» Dual innervation of many organs ² having a brake and an accelerator provides more control
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.
transmitters carry the signal across synapses y Chemical transmitters are made and stored in the presynaptic terminal y The transmitter diffuses across the synaptic gap and binds to a receptor in the postsynaptic membrane. y Binding of the Transmitter Produces an excitatory postsynaptic potential EPSP or inhibitory postsynaptic potential IPSP
The Transmitter is Broken down and Recycled y Once the signal has been delivered the transmitter must be removed so that new signals may be received y In some cases the transmitter is broken down by an enzyme in the synapse y In other cases the transmitter is recycledit is transported back into the presynaptic nerve y In still other cases these 2 methods are combined
Acetylcholine y Important neurotransmitter in central and peripheral nervous systems. y 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 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. y Ca++ recat with synapsin that bind the vesciles, which on its unbinding the vesciles sweeps to attach to the presynaptic membrane. y The vesciles rupture and the acetylcholine released to the synaptic cleft. y 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 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). y Two types of cholinergic receptors are well known: y Nicotinic receptors which are easily activated by agonist molocule such as nicotine and y Muscarinic receptors: which are sensitive to muscarine.
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).
Located in the ganglia of both the PSNS and SNS y Named ³nicotinic´ because can be stimulated by the alkaloid nicotine
Smooth muscle Cardiac muscle Glands of parasympathetic fibers Effector organs of cholinergic sympathetic fibers
Named ³muscarinic´ because can be stimulated by the alkaloid muscarine
Parasympathetic (Cholinergic) Drugs
Subdivisions of the Autonomic Nervous System
Primary Neurotransmitter Receptors & Second Messenger Systems
norepinephrine epinephrine (~20%) Adrenergic GPCRs E1 ± IP3/DAG, o[Ca2+]i oPKC E2 - qcAMP/PKA
F1 - ocAMP/PKA F2 - ocAMP/PKA F3 - ocAMP/PKA
Muscarinic GPCRs M1 ± IP3/DAG, o[Ca2+]i oPKC M2 ± qcAMP/PKA, oPI(3)K M3 ± qcAMP/PKA, IP3/DAG, o[Ca2+]i oPKC M4 ± M5 ± IP3/DAG, o[Ca2+]i oPKC
Adrenal Medulla (epi:norepi::80:20)
Comparison of sympathetic and Parasympathetic Pathways
Neurotransmitters y 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.
Drugs that stimulate the parasympathetic nervous system (PSNS). y Drugs that mimic the effects of the PSNS neurotransmitter y Acetylcholine (ACh)
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).
x - 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.
These drugs which antagonize the action of Ach by one of the following mechanisms:y Competitive inhibition: These drugs occupy the Ach receptors and present its action. y Persistent depolarization: These drugs cause prolonged depolarization of Ach receptor thus they prevent the excitation of the receptor by the released Ach.
Muscarinic like action blockers These drugs block the action of Ach at cholinergic receptors by blocking the action of Ach at muscarinic receptors e.g.AtropineHomatropine Hyoscine 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. -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
- Ganglion blocker used - Curare is used as a for blocking conduction in muscle relaxant sympathetic ganglion of hypertension.
Sympathetic (Adrenergic) Drugs
from phe, diet, or protein breakdown
BH4 Tyrosine 1
BH2 L-Dopa Tyrosine hydroxylase 2 CO2
(rate-determining step) H O 2
DPN OHase in neuroscretory granules
Dopa decarboxylase pyridoxal phosphate
Norepinephrine Dopamine hydroxylase PNMT Epinephrine 4 SAM SAH
PNMT specific to adrenal medulla
Parkinson¶s 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.
tress Chronic regulation Hypothalamus ACTH Cortisol Tyrosine
from adrenal cortex via intraadrenal portal system
.... . ... .... ... ...
DPN q NE
Epinephrine neurosecretory granules
acetylcholine Adrenal Medulla Chromaffin Cell promotes exocytosis E EEE NE E E NE EE
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 (E1) alpha2 (E2) beta1 (F1) beta2 (F2) Agonists E>NE NE>E E=NE E>>NE Second Messenger IP3/Ca2+; DAG
q cyclic AMP o cyclic AMP o 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
Figure 4. Model for the structure of the F2-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)
E1-receptor E 2receptor F 1receptor F2-receptor
Process (IP3, DAG) Carbohydrat o liver e glycogenolysis metabolism Fat metabolism Hormone secretion No effect No effect Smooth muscle - blood vessels, genitourinary tract
(q cAMP) No effect
(o cAMP) No effect
oliver/muscle glycogenolysis; o liver gluconeogenesis; q glycogenesis
q lipolysis q insulin secretion
o insulin and glucagon secretion
Smooth muscle some vascular; GI tract relaxation
Myocardial -o rate, force
Smooth muscle relaxation - bronchi, blood vessels, GI tract, genitourinary tract
F1 or F2 receptor
GTP \ GTP
inactive adenylyl cyclase ATP
ACTIVE adenylyl cyclase
inactive adenylyl cyclase
Figure 5. Mechanisms of F1, F2, and E2 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 o hepatic glycogenolysis/ gluconeogenesis preserves glucose for CNS by q insulin release leading to reduced glucose uptake by muscle/ adipose increases cardiac output norepinephrine elicits responses of the CV system - o blood flow and q insulin secretion.
Figure 6. Mechanisms for terminating the signal generated by epinephrine binding to a F-adrenergic receptor epinephrine  dissociation
degradation to VMA
 GTPase 
ATP cAMP AMP phosphodiesterase
activated PKA phosphorylates enzymes
OP OP phosphorylation of F-receptor by F-ARK decreases activity even with bound hormone
OPOP binding of F-arrestin further inactivates receptor despite bound hormone
insulin activation of protein phosphatase to dephosphorylate enzymes
&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)