INTRODUCTION TO

AUTOMOMIC PHARMACOLOGY:
Part I: Why study autonomic pharmacology?

Autonomic Pharmacology
is Rewarding!!
LOGICAL
CLINICALLY
RELEVANT

Autonomic Pharmacology is Logical

Mechanism
of Drug Action

Anatomical,
Physiological &
Neurobiological
Information

Predict
Effects of Drugs

Autonomic Pharmacology is Logical

Drug A blocks
receptors for
neurotransmitter X

Nerves to organ Y
release neurotransmitter X,
and X increases
the activity of organ Y

Drug A decreases
activity of
organ Y

Autonomic Pharmacology
is Clinically Relevant

Autonomic drugs are used for the

treatment of

Angina

Autonomic drugs are used for the

treatment of

Heart Failure

Autonomic drugs are used for the

treatment of

Alzheimers Disease

Autonomic drugs are used for the

High Blood
Pressure

treatment of

Autonomic drugs are used for the

treatment of

Benign Prostatic Hypertrophy

Autonomic drugs are used for the

treatment of

Anaphylactic Shock

Autonomic drugs are used for the

treatment of

Septic Shock

Autonomic drugs are used for the

treatment of

Asthma

INTRODUCTION TO
AUTONOMIC PHARMACOLOGY: Part II
Anatomy of peripheral nervous system

Peripheral Nervous System

Somatic Nervous
System

Autonomic Nervous
System

Parasympathetic
Sympathetic
Nervous System Nervous System
Selective
Activation
Skeletal
Muscle

Diffuse
Activation

Glands, Smooth Muscle

& Cardiac Muscle

Peripheral Nervous System

Controls
skeletal
muscle
Somatic
Nervous
System

One
Neuron
Efferent
Limb

Controls
smooth &
cardiac
muscle &
glands
Autonomic
Nervous
System

Two
Neuron
Efferent
Limb

Somatic

Ganglion

Sympathetic
Parasympathetic

Preganglionic Fiber;
Cholinergic

Ach

Sympathetic

Skeletal
Ach Muscle

Smooth Muscle
Postganglionic Fiber; Cardiac Cells
NE
Adrenergic
Gland Cells

Ganglion
Ach

Postganglionic
Fiber; Cholinergic

Sympathetic

Motor Fiber

Ach

Sweat
Glands

EPI/NE

Ach

Adrenal Gland

Ganglion
Ach

Smooth Muscle
Cardiac Cells
Gland Cells
Ach

Sympathetic Nervous System

(Thoracolumbar Outflow)
Pilomotor Muscles
Sweat Glands

Blood Vessels

Radial Muscle of Iris

Ciliary Muscle
Sublingual/Submaxillary
& Parotid Gland
SA & AV Nodes
His-Purkinje System
Myocardium
Bronchi/Bronchial
Glands
Stomach
Kidneys
Intestines

Paravertebral Ganglia
Prevertebral Ganglia

Bladder//Genitalia

White Ramus Communicans

Gray Ramus Communicans
Spinal
Nerve

Ventral Root

Autonomic
Nerve

Paravertebral
Ganglion
Prevertebral
Ganglion

ADRENAL MEDULLA

Chromaffin Cells

Epinephrine
(+) Dilates Airways

(+) Cardiac Output

(+) Muscle Contraction & Efficiency

(+) Fatty Acid Release

(+) Mental Alertness

(+) ACTH & TSH

(+) Glycogenolysis

(-) Intestinal Motility

Parasympathetic Nervous System (Craniosacral Outflow)

SA & AV Node
Sphincter Muscle of Iris
Ciliary Muscle

Bronchi/Bronchial
Glands
Stomach
Small Intestines

Lacrimal Gland

Submaxillary &
Sublingual
Glands
Parotid Gland

Bile Ducts
Gallbladder
Kidney
Large Intestines
Bladder
Genitalia

Most organs receive dual sympathetic

and parasympathetic innervation.
However, some organs only receive
sympathetic innervation:
Spleen
Sweat Glands
Piloerector Muscles
Most Blood Vessels

INTRODUCTION TO
AUTONOMIC PHARMACOLOGY: Part III
Mechanism of neurotransmission at
in the autonomic nervous system

General Features of Peripheral

Autonomic Neurotransmission

NT = Neurotransmitter

General Features of Peripheral

Autonomic Neurotransmission
Nerve Impulse
Membrane Depolarization of
Pre- or Postganglionic Fiber
Calcium Entry into
Varicosity
Exocytosis of NT

Depolarization of Postganglionic
Fiber or Response of
Effector Cell
Activation of NT
Receptors
Diffusion of NT Across
Neuroeffector Junction
or Synapse

SUMMARY OF ADRENERGIC NEUROTRANSMISSSION

COMT

Sympathetic Postganglionic Fiber

Effector Cell

Neuroeffector Junction
(Liver)

Summary of Catecholamine Biosynthesis

Tyrosine

DOPA

Dopamine

Norepinephrine

SYMPATHETIC
NERVE
ADRENAL
GLAND

Epinephrine

SUMMARY OF CHOLINERGIC NEUROTRANSMISSSION

Neuroeffector Junction

Parasympathetic/Sympathetic
Preganglionic Fiber or
Parasympathetic Postganglionic Fiber

Parasympathetic or
Sympathetic
Postganglionic Fiber
or Effector Cell

COTRANSMISSION
Release of More Than One
Neurotransmitter from the Same
Nerve Terminal
Cotransmitter A

Cotransmitter B

Synergistic or Opposite Actions

Types of Postsynaptic Synergism

Norepinephrine/NPY
Norepinephrine/ATP

Perfusion Pressure
(mmHg)

Example of Postsynaptic Synergism:

(NPY enhances actions of NE)

NPY 10 nM
NE

NE

Example of Postsynaptic Synergism:

ATP mediates fast response
NE mediates slow response
Control
Prazosin
Prazosin +
Suramin
Control
Suramin
Prazosin +
Suramin

Many Examples of NANC Neurotransmitters

Many Examples of NANC Neurotransmitters

MODULATION OF NEUROTRANSMISSION
Modulation of
Neurotransmisson
Presynaptic/
Prejunctional
Modulation
Presynaptic/
Prejunctional
Inhibition

Presynaptic/
Prejunctional
Facilitation

Postsynaptic/
Postjunctional
Modulation
Postsynaptic/
Postjunctional
Postsynaptic/ Inhibition
Postjunctional
Facilitation

MODULATION OF NEUROTRANSMISSION
Sources of
Modulators of
Neurotransmission
From Nerve
Terminal Being
From
Modulated
Postsynaptic/
(e.g.,
Postjunctional
Autoinhibitory Site (e.g., TransFrom
Feedback)
synaptic/
Nearby
Transjunctional
Nerve
Inhibitory
Terminal
Feedback)
(Crosstalk)

From
Remote
Site via
Circulation
(e.g., Renin
Release)

NE

Mechanisms of Neuromodulation

NE

Ach

Ang II

Mechanisms of Neuromodulation

Epi

INTRODUCTION TO
AUTONOMIC PHARMACOLOGY: Part IV
Adrenergic and cholinergic receptors

Adrenergic Receptors: Receptors Activated by EPI/NE

-adrenergic
receptors

(Epinephrine>Isoproterenol)
1-adrenergic
receptors
(Phenylephrine>Clonidine)
2-adrenergic
receptors
(Clonidine>Phenylephrine)

-adrenergic receptors
(Isoproterenol>Epinephrine)
1-adrenergic
receptors
(EPI = NE)
2-adrenergic
receptors
(EPI>NE)
3-adrenergic
receptors
(NE>EPI)

Adrenergic Receptors:
Signal Transduction

Signal Transduction by 1 - Adrenergic Receptors

Gq
q

Signal Transduction by 2 - and - Adrenergic Receptors

Cholinergic Receptors: Receptors Activated by Ach

Muscarinic Receptors
(Activated by muscarine from Amanita muscaria)
(D
e fi
Nicotinic Receptors
ne
db
(Activated by nicotine from tobacco)
M1
yM
(Nerve Cells)
ole
cu
M2
lar
NM
(Heart & SM)
Cl
on
(Neuromuscular)
i ng
M3
(Blocked by
)
NN
(Heart & SM)
Tubocurarine) Autonomic ganglia,
M4
Adrenal medulla &
CNS
(SM & Glands) M
5
(Blocked by Trimethaphan)
(?)

Cholinergic Receptors:
Signal Transduction

Muscarinic Receptors
Gq
Activation of PLC

Gi

Formation
of IP3

Formation
of DAG

subunit

Release of
Intracellular
Calcium

Activation of
PKC

Inhibition of
Adenylyl
Cyclase

subunit
Opening of
Potassium
Channels

INTRODUCTION TO
AUTONOMIC PHARMACOLOGY: Part V
Actions of autonomic nerves:
Adrenergic and cholinergic responses

Summary of Adrenergic and Cholinergic Responses

Normal:
Ciliary Muscle Relaxed
Suspensory Ligaments Under Tension
Lens is Flattened
Focus on Distant Objects

Accommodation:
Ciliary Muscle Contracts
Reduced Tension on Suspensory Ligaments
Lens becomes Round
Focus on Near Objects

Summary of Adrenergic and Cholinergic Responses

Summary of Adrenergic and Cholinergic Responses

Summary of Adrenergic and Cholinergic Responses

EDRF
Injected Ach

EDRF (NO)