Transcript Introduction to Autonomic Nervous System

Introduction to
Autonomic Nervous
System
Pawitra Pulbutr
M.Sc. In Pharm
(Pharmacology)
Objectives
สามารถอธิบายพื้นฐานทางกายวิภาคและสรีรวิทยาของระบบประสาท
ซิมพาเทติก รวมทัง้ เป้ าหมายการออกฤทธิ์ของยาที่มีผลต่อระบบ
ประสาทซิมพาเทติก
สามารถอธิบายพื้นฐานทางกายวิภาคและสรีรวิทยาของระบบประสาท
พาราซิมพาเทติก รวมทัง้ เป้ าหมายการออกฤทธิ์ของยาที่มีผลต่อระบบ
ประสาทพาราซิมพาเทติก
Motor (Efferent) portion of
nervous system
Autonomic portion… Autonomic
Nervous System (ANS)
Involuntary control
CVS, GI, Iris, Genitourinary function
Somatic portion
Voluntary control
Commanded by brain
Posture/ Movement
Muscle
>>>
Skeletal
Preganglionic neuron
Postganglionic neuron
Difference between ANS VS Somatic nervous system
Drugs acting on ANS
Act on receptor of NTs
Agonist
Antagonist
Interfere biosynthesis of NTs
Inhibit precursor uptake
Inhibit enzyme for biosynthesis
Interfere degradation of NTs
Inhibit degradation enzyme
Inhibit NTs reuptake
Autonomic Nervous System
(ANS)
Sympathetic Nervous System
(Thoracolumbar division)
Parasympathetic Nervous System
(Craniosacral division)
Named after anatomy origin NOT
after type of action or NTs !!
Medullary
Cervical
Thoracic
Lumbar
Sacral
Basic plan of ANS
Enteric Nervous System (ENS)
A highly simplified diagram of some of the circuitry of the
enteric nervous system (ENS)
Neurotransmitters of ANS
Major (Primary) NTs
Acetylcholine (ACh)
“Cholinergic fiber”
Norepinephrine (NE)
”Noradrenergic or Adrenergic fiber”
Co-transmitters
Peptide, etc.
Cholinergic fiber
Synthesis & release ACh
All Pre-ganglionic autonomic fiber
(both SNS & PNS)
Somatic fiber (innervate skeletal M.)
All Parasympathetic postganglionic
fiber
Some sympathetic postganglionic
fiber (innervate eccrine sweat gland)
Adrenergic fiber
Synthesis & release NE
Most Postganglionic sympathetic
fiber
Adrenal medulla = Modified
postganglionic sympathetic neuron
release both NE & Epinephrine (Epi)
Hemicholiniums
precursor
Action
potential
Choline acetyl
transferase (ChAT)
vesamicol
Cholinergic
transmission
ACh receptor =
Cholinergic receptor
Postsynaptic RC
>>> Action
Presynaptic RC
Botulinum
toxin
AChE
Autoreceptor
Heteroreceptor
Acetylcholine
AChE
enzyme
Anionic
site
Esteratic
site
Acetylated enzyme
Free AChE
ACh
hydrolysis
via AChE
Tyrosine
RLS
Tyrosine
hydroxylase
Metyrosine
Dopamine hydroxylase
Reserpine
Action
Potential
Bretylium/
Guanethidine
Adrenergic
transmission
Cocaine /
Tricyclic
antidepressant
(TCA)
Metabolism via
MAO & COMT
1
2
Degradation of NE
Less are metabolized in synaptic cleft
Major degradation
Simple diffusion away from synapse
Metabolize in plasma & liver
Uptake via uptake
Uptake 1 into presynaptic nerve
Uptake 2 into perisynaptic glia &
smooth muscle
Drugs acting on adrenergic
transmission
Direct acting
Adrenergic Agonist
Adrenergic Antagonist
Indirect acting… increase NE at
synaptic cleft
Reuptake inhibitors
Cocaine, TCA
Increase NE release from vesicle
Amphetamine, Tyrosine
Autonomic receptor
Acetylcholine receptor
(Cholinergic receptor)
Nicotinic receptor (N receptor)
NN, NM
Ion channel linked receptor
Muscarinic receptor (M receptor)
M1, M2, M3
GPCR
Noradrenergic receptor
(Adrenergic receptor)
Alpha receptor
Alpha1, Alpha2
GPCR
Beta receptor
Beta1, Beta2, Beta3
GPCR
Direct effects of ANS activity
on some organ systems
Organ
Effect of
Sympathetic Activity
Action
Receptor
Parasympathetic
Activity
Action
Receptor
Eye
Iris
Radial muscle
Circular muscle
Ciliary muscle
Heart
Sinoatrial node
Ectopic
pacemakers
Contractility
Contracts
….
[Relaxes]
1
….

….
Contracts
Contracts
….
M3
M3
Accelerates
Accelerates
1,2
1,2
Decelerates M2
….
….
Increases
1,2
Decreases
(atria)
M2
Organ
Effect of
Sympathetic Activity
Action
Blood vessels
Skin, splanchnic
vessels
Skeletal muscle
vessels
Endothelium
Receptor
Contracts 
2
Relaxes
[contract 
M*
]
Relaxes
Bronchiolar
Relaxes
smooth muscle
GI tract
2
Smooth muscle
2#, 2
Relaxes
Walls
Contracts 1
Sphincter
….
….
Secretion
Myenteric plexus
Parasympathetic
Activity
Action
Receptor
….
….
….
….
….
….
….
….
Release
EDRF
M3**
Contracts M3
Contracts
Relaxes
Increases
Activates
M3
M3
M3
M1
Organ
Effect of
Sympathetic Activity
Action
Genitourinary
smooth muscle
Parasympathetic
Activity
Receptor
Action
Receptor
Relaxes
Contracts
Relaxes
Contracts
Ejaculatn
2
1
2


Contracts
Relaxes
…
Contracts
Erection
M3
M3
….
M3
M
Contracts

Thermoregulatory Increases
Apocrine (stress) Increases
M

…
…
…
…
…
…
Bladder wall
Sphincter
Uterus, pregnant
Penis, Seminal
vesicle
Skin
Pilomotorsmooth
muscle
Sweat glands
Organ
Effect of
Sympathetic Activity
Action
Metabolic
functions
Liver
Liver
Fat cells
Kidney
Autonomic nerve
endings
Sympathetic
Parasympathetic
Activity
RC
Action
Receptor
Gluconeogenesis
Glycogenolysis
Lipolysis
Renin release
2,
2,
3
1
…
…
…
…
…
…
M##
Decrease
NE release
…
…
Parasympathetic Decrease ACh
release

…
…
…
…
Baroreceptor Reflex Chart
Stand up quickly
BP falls in upper body
Aortic Arch
Carotid Sinus
Medulla
Oblongata
Nucleus Tractus
Solitarius
Neutral Integration
Effectors
Veins &
Arterioles
Vasoconstriction
Increased TPR
Heart Muscle
Increased SV
SA node
Increased HR
Increased CO
Increased BP = CO x TPR
BP = TPR * CO
CO = HR * SV
SV = Contractility force * Venous return
Venous return = Venous tone * Blood volume
Autonomic and
Hormonal Control of CVS function
Blood volume = Aldosterone regulation
Presynaptic regulation
Negative feedback control
“Autoreceptor”
Receptor of their own secreted NTs
Alpha 2-receptor at presynaptic nerve
Inhibit NE release from presynaptic
“Heteroreceptor”
Receptor of other NTs
Cholinergic receptor at sympathetic
nerve
Inhibit NE release from presynaptic
Postsynaptic regulation
Receptor dynamic
Receptor upregulation
Surgical denervation… increase No. of RC
Increase response … “denervation
supersensitivity”
Pharmacologic denervation supersensitivity
… drug that decrease NTs >>> reserpine
Receptor downregulation
Receptor desensitization
Main process of
transmitters
1.
uptake of precursors
2.
synthesis of transmitters
3.
storage in vesicle
4.
degradation of surplus
5.
depolarization
6.
Ca++ influx
7.
exocytosis
8.
diffusion to postsynp RC
9.
activation of postsynp RC
10. inactivation of transmitters
11.
reuptake or degradation
12.
interact with presynp RC