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PHARMCOL201 2005: lecture 14

Introduction to the autonomic Learning Objectives


nervous system • By the end of the lecture you should be able to:
• Describe the sites of drug action on a nerve terminal
Lecture 14 • Describe the anatomy and chemistry of the autonomic
nervous system
• Describe the actions of the autonomic nervous system
Rang, Dale and Ritter • Define with examples the principles of
5th Edition, Chapter 9 neuromodulation: heterotropic and homotropic
presynaptic inhibition, and cotransmission

Neural Transmission P P Ca2+

T
• The junction of an axonal ending with a nerve cell,
a muscle cell or a glandular cell is called a T
synapse.
• Neurotransmitters are synthesised and stored in
vesicles in the nerve terminal and then released
into the synapse. D T T
• Transmitter action must then be terminated by ENZYME
either metabolism or transport of the transmitter.

Schematic of nerve terminal

Action potential
4

At what points might we change P


1
P 2 Ca2+

the normal events of synaptic T 3


5

neurotransmission? T
6
8
There are 10 potential places for 10
a drug to act. D T T
9
ENZYME

7
PHARMCOL201 2005: lecture 14

The Nervous System


SKELETAL MUSCLE
Function of the ANS
TIC • ANS can be divided into two parts which in
MA
Joints SO TOR general have opposing actions:
Skin MO
SOMATIC
Skeletal muscle
CNS • PARASYMPATHETIC: accumulation,
AU storage and preservation of resources.
T ON
OM • SYMPATHETIC: prepares the body for
IC
GLANDS strenuous activity, stress emergencies.
AFFERENT SMOOTH MUSCLE (Fight or flight)
HEART MUSCLE

EFFERENT

Basic anatomy of the ANS


ANS FUNCTION
GANGLION
• PARASYMPATHETIC • SYMPATHETIC
• Accelerates heart rate
• heart rate • blood flow through skeletal
• GI activity muscle
• blood flow through skin,
• Pupils constrict visceral organs.
• Glands stimulated to • GI tract activity
PRE-GANGLIONIC POST-GANGLIONIC
secrete (mucous, saliva). • Pupils dilate NEURON NEURON
• glycogen breakdown.
• Increased lipid breakdown.

ANS Receptor Types


• Parasympathetic • Sympathetic
• Primary transmitter, • Preganglionic: Ach
Ach • Postganglionic: NA
• Nicotinic: Ng & Nm • Preganglionic: Ng
• Muscarinic: M1, M2 • Postganglionic: α1 &
& M3 α2, β1& β2

For more detail please see P127, RDRM Table 9.1 (slide that gives function
Earlier in the presentation).

Rang, Dale and Ritter, “Pharmacology” 4th Edition page 96


PHARMCOL201 2005: lecture 14

Chemistry of the Peripheral Chemistry of the Peripheral


Nervous System Nervous System

SKELETAL
SOMATIC ACh N MUSCLE
PARASYMP ACh N ACh M
SM. MUSCLE
Note: This is the SOMATIC nervous system, not part CARDIAC
of the Autonomic nervous system
GLANDS

Chemistry of the Peripheral Neuromodulation


Nervous System • Term was coined to describe the effects of
chemical mediators on presynaptic terminals
SYMP. ACh N ADRENAL
MEDULLA – Mediators act to increase or decrease the efficacy of
synaptic transmission without participating directly
SMOOTH MUSCLE as a transmitter.
SYMP. ACh N NA CARDIAC
GLANDS • But also happens post-synaptically
– Eg neuropeptides act on ion channels to increase or
decrease excitability and thereby control the firing
SWEAT GLANDS pattern of the cells
SYMP. ACh N ACh M PILOERECTOR

A
General principles of Chemical
Transmission
• Neuromodulation:
– presynaptic feedback inhibition (homotropic: the
transmitter acts on a presynaptic receptor to inhibit
its own release) B

– Heterotropic presynaptic inhibition – another


transmitter acts on a presynaptic receptor to inhibit
the release of the neurotransmitter. (see Fig 9.4
RDRM, P129)
PHARMCOL201 2005: lecture 14

Pre-Synaptic Receptors
• Because the pre-synaptic receptors are NANC & Cotransmission
pharmacologically distinct from the post-
synaptic receptors, specific agonists and • Drugs that abolish the responses to
antagonists exist to these receptors. acetylcholine and noradrenaline do not
• Alpha-2 adrenergic receptor blockade (e.g. completely block autonomic transmission.
yohimbine) results in a 10 fold increase in NA
release in response to stimulation. • Single nerve terminals may store &
• There are several other presynaptic influences
release more than one neurotransmitter,
on noradrenergic or cholinergic transmission. e.g. ATP & NA.
• See RDRM P132, Fig 9.7

Examples of NANC Transmitters