Review of the

Autonomic Nervous System

Part 1

Thomas E. Tenner, Jr., Ph.D.

Dept. of Medical Education
Dept. Pharmacology & Neuroscience
[email protected]
743-7169

1
Recommended Background Reading :

Chapter 6
“Introduction to Autonomic Pharmacology”
Basic and Clinical Pharmacology
Bertram Katzung
(13th Edition)

2
 Learning Objectives:

Be able to:
1) Describe the functions of the sympathoadrenal (SAS) and
parasympathetic (PNS) systems of the Autonomic Nervous
system, and their interactions.
2) Name the major cholinoceptors and adrenoceptors of the
Autonomic Nervous System and identify their important
receptor subtypes.
3) Associate the actions of membrane receptor subtypes with
appropriate “second messenger” systems.
4) Describe the interplay of SAS and PNS
5) Explain Autonomic control of Blood Pressure

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FUNCTION OF THE ANS

4
Peripheral Nervous System
Somatic Nervous Autonomic Nervous
System System

Parasympathetic Sympathetic
Nervous System Nervous System

Discrete Diffuse
Activation Activation
Skeletal
Muscle
Glands, Smooth Muscle
& Cardiac Muscle 5
 Parasympathetic System:
‘Trophotropic’
• Rest and Digest - Maintains essential body
functions and IS essential for life:
– Protects the Eye
• Constriction of the pupils (Miosis), Near vision
(Accommodation), Lacrimation
– Protects Heart
• Bradycardia
– Protects the Respiratory System
• Broncho-constriction / Broncho-secretion
– Aids in Digestion:
• Salivation, Peristalsis, Gastric acid secretion
– Aids in Urination, Defecation
– Aids in Procreation 6
 SympathoAdrenal System:
‘Ergotropic’
• Fight or Flight - used to adjust the body to
stressful situations but is not needed for life:
– Dilation of pupils (Mydriasis)
– Dilation of bronchi, (↓) nasal, pulmonary secretions
– (↑) heart rate and BP
– (↓) blood flow to the skin and internal organs
– (↑) blood flow to skeletal muscles, brain, and heart
– Mobilize energy stores
– Inhibits Urination, Defecation
– Aids in Procreation
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8
 DESCRIBE THE
NEUROCHEMISTRY OF
ACETYLCHOLINE,
NOREPINEPHRINE, AND
EPINEPHRINE

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 Cholinergic
Neurotransmission
• Synthesis
Choline Acetyl Transferase
• Storage
Vesicles
• Release – Na+ / Ca2+
• Receptor Activation
Musc / Nic
• Termination of Action
Acetyl cholinesterase

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 Adrenergic Neurotransmission

•Synthesis
Tyrosine Hydroxylase**
Dopadecarboxylase
• Storage
Dopamine- hydroxylase
• Release – Na+ / Ca2+
• Receptor Activation:
1,,1
• Autoreceptor Activation
2 ,
• Termination of Action:
Diffusion / COMT / MAO
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AUTONOMIC RECEPTORS
AND
SIGNAL TRANSDUCTION
MECHANISMS

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 Autonomic Receptors:
• Cholinoceptor (acetylcholine)
Nicotinic – ionotropic (n, m)
Muscarinic – G-protein coupled (M1-5)
• Adrenoceptor (epinephrine, norepinephrine)
Alpha (α1ABD, α2ABC): G-protein coupled
Beta (β1-3): G-protein coupled
Dopaminergic receptors (dopamine)
D1-5 (2S, 2L): G-protein coupled
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 Nicotinic
receptors:

ion
channel

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Muscarinic
receptors:
G-protein
coupled

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 Raymond Ahlquist (1948)
• “Alpha receptors are excitatory
everywhere but the gut”

• “Beta receptors are inhibitory everywhere

but the heart”

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Adrenergic Neurotransmitters:
Rank Order of Potency

– Isoproterenol: β 1 = β 2 = β 3 >>>> α1 = α2

– Norepinephrine : α1 = α2 = β 1 = β 3 >>>> β 2

– Epinephrine: α1 = α2 = β 1 = β 2 = β 3

– Dopamine : DA 1> β 1> α1

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Adrenergic Receptors: Receptors Activated by EPI/NE

α-adrenergic receptors β-adrenergic receptors

a
(Epinephrine>Isoproterenol) (Isoproterenol>Epinephrine)

α 1-adrenergic
receptors β 1-adrenergic
(Phenylephrine>Clonidine)
receptors
(EPI = NE)

β 2-adrenergic
receptors
(EPI>NE)

α 2-adrenergic β 3-adrenergic
receptors receptors
(Clonidine>Phenylephrine) (NE>EPI)
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Signal Transduction by 1 - Adrenergic Receptors

Gq

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Signal Transduction by 2- and -Adrenergic Receptors

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INTERPLAY OF SAS AND PNS

1) Neuromodulation
• Presynaptic receptors
2) Physiological Antagonism
• HR
• Iris
3) Physiological Cooperation
• Male reproduction
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Mechanisms of Neuromodulation

Epi

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Mechanisms of Neuromodulation

NE

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Autonomic control in the eye:

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Baroreflex:

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 Control of Blood Pressure

Arterial - Afterload
mABP = CO x TPR

Cardiac - HR SV
Chronotropy

Cardiac - Inotropy CF VR 27
Venous – Preload
Drugs to know…

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Process Affected Drug Example Site Action
Transmitter Reserpine Adrenergic vesicles Depletes NE,DA
Storage (Also Epi from
Adrenal Medulla)
Transmitter NE/EPI/ACh/ Activate/block Pre- Modulate release
Release ANG-II* junctional receptors
(See Slide 20) at Adrenergic/Cholin-
ergic terminals
Botulinum Toxin Cholinergic terminals Prevents release
Alpha- Cholinergic terminals Explosive release
Latrotoxin**
Amphetamine/ Adrenergic vesicles Promotes release
Tyramine
Transmitter Cocaine, Adrenergic terminals Inhibit reuptake
Reuptake TCA’s/SNRIs***
Enzymatic Neostigmine Acetylcholinesterase Intensifies Ach
Inactivation of Inhibitor action at
Transmitter Muscarinic and
Nicotinic receptors
Tranylcypromine MonoAmineOxidase Intensifies NE/DA
(MAO) Inhibitor action.
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