By Duy Thai, 1997 Pharmacology Semester 1 page 1 of 4

PRINCIPLES OF NEUROTRANSMISSION

• In pharmacology, we are interested in the target organ (e.g. skeletal muscle). If we know which organ is targeted by
nerves, we can find drugs that can alter the function of the organ.

CNS
Brain &
Spinal cord

Autonomic Somatic
(involuntary) (voluntary)

Skeletal muscle

Sympathetic Parasympathetic

Enteric

The autonomic nervous system

• The ANS is essentially a 2 fibre system, with preganglionic fibres leaving the CNS to synapse with postganglionic
fibres in the autonomic ganglia.
Ganglion

Preganglionic fibre Postganglionic fibre

• There are 2 divisions of the autonomic nervous system (3 if you include the enteric)
1. Parasympathetic
• Anatomically, the parasympathetic fibres are located craniosacrally in the spinal cord
• The have long preganglionic fibres
• Short postganglionic fibres, with the ganglion close to or in the target tissue
2. Sympathetic
• Anatomically, are located in the thoracolumbar portion of the spinal cord
• Have short preganglionic fibres which synapse in ganglia which form a chain - the sympathetic
trunk.
• The postganglionic fibres leave this chain and head off to the tissues. Hence, they tend to be
relatively long.
• Most tissues are innervated by both parasympathetics and sympathetics nerves, however there are some exceptions
to this:
• Tissues predominantly sympathetic nerves:
• Blood vessels
• Skin
• Kidney, liver
• Adipose tissue
• Tissues predominantly parasympathetic nerves:
• Bronchi (note that you can have sympathetic stimulation of bronchi via adrenaline - not by direct
nervous stimulation)
• There are also some exceptions to the general layout of the autonomic fibres:
• Some sympathetic preganglionic fibres may pass right through the sympathetic trunk without synapsing
and go directly to the gut where there is a sympathetic ganglion in the viscera.
By Duy Thai, 1997 Pharmacology Semester 1 page 2 of 4

• There is a single sympathetic fibre which goes directly to a tissue without synapsing - the tissue is the
adrenal glands, which when stimulated release noradrenaline and adrenaline.

Chemical transmission
• How does information travel from the brain to the target?
• Electrical transmission via action potentials transmit messages down a nerve fibre
• Chemical transmission is used to transmit signals from neuron to neuron via the synapse.
• Evidence for chemical transmission was based on the fact that the presynaptic terminal had a
morphology similar to a hormone secretory cell. It contained vesicles which presumably
contained chemicals which could be exocytosed into the synaptic cleft to act on the post synaptic
terminal
• For chemical transmission to be accepted, it was not good enough to say that the chemical was there . There needed
to be more evidence to show that:
1. The nerve can synthesise the chemical de novo
2. The nerve can store the chemical
3. There must be some way of being able to release the chemical
4. The chemical needs to have a receptive site on the target
5. The chemical needs to be able to be inactivated via:
• Metabolism
• Reuptake

The blending of anatomy with pharmacology

• All parasympathetic post ganglionic fibres contain acetylcholine (Ach)
• Most sympathetic postganglionic fibres contain noradrenaline (NA)
• The exception is postganglionic fibres innervating the skin, which use Ach
• All preganglionic fibres (both sympathetic and parasympathetic) contain Ach
• In the somatic nervous system, only a single fibre goes straight to the skeletal muscle and releases Ach.
• We can therefore make a generalisation that all peripheral fibres leaving the spinal cord release acetylcholine

Physiology of the autonomic nervous system

• The autonomic nervous system regulates involuntary functions which have a role in homeostasis.
• Generally, it can be said that:
• Parasympathetics are involved with anabolic processes, rest and repose
• Sympathetics are involved with catabolic processes, flight and fright
• Parasympathetics
1. Decrease heart rate
2. Noisy breathing (bronchial constriction)
3. Small pupils (contraction of the circular muscle)
4. Increased salivation
5. Increased gut motility
• Sympathetics
1. Increased heart rate and force of contraction
2. Blood vessels constrict (especially in the skin and viscera)
• When you are nervous your skin feels cold and you stomach feels tight (due to reduced blood
volume going to the gut and making it anoxic - not because the gut is constricting, which is
parasympathetics)
3. Skeletal muscle blood vessels dilate so muscles can get more blood
4. Pupils dilate (contraction of radial muscles)
5. Bronchioles dilate
• This is not due to a direct innervation by sympathetic nerves. Instead, adrenaline released from
the adrenal glands cause the dilation
6. Blood sugar rises
7. Hair becomes erected on skin

The blending of physiology with pharmacology

• The effects are due to the neurotransmitter released from the postganglionic fibres activating specific receptors on
the target tissues.
• Postganglionic parasympathetic fibres
By Duy Thai, 1997 Pharmacology Semester 1 page 3 of 4

• All fibres release Ach

• The receptors for Ach in the tissues are muscarinic receptors
• Postganglionic sympathetic fibres
• Release mainly noradrenaline
• The receptors for noradrenaline (and adrenaline) in the tissues are α and β receptors
• Generally, α effects cause constriction, β effects cause dilation
• Preganglionic fibres
• All release Ach
• The Ach acts on nicotinic receptors which are located on postganglionic nerve cell bodies and also in
skeletal muscle.

N Heart
Ach Ach
Parasympathetic M GIT
Bronchi
N
Ach Ach
M Sweat glands

Sympathetic N Heart
Ach Noradrenaline
α, β GIT
Blood vessels
Ach N
Adrenal release of NA
and adrenaline

Somatic Ach N Skeletal muscle

Nicotinic receptors
• Can mimic the sympathetic or parasympathetic system, depending on where the agonist is placed.
• If the agonist is placed in the sympathetic trunk, then most likely you would get a sympathetic response
• If the agonist was placed in the tissues, which is where the parasympathetic ganglia are located, you would
get a parasympathetic response
• If an agonist is placed on skeletal muscle, contraction of skeletal muscle can occur

Muscarinic receptors
• Heart Decrease rate and force
• Bronchi Constriction The ones in bold are supplied
predominantly by parasympathetics
• GIT Increased motility, dilation of sphincters
• Pupil Constriction
• Glands Secretion

Adrenoreceptor activation
• α adrenoreceptors
• Blood vessels Constriction (control of BP)
• GIT Constrict sphincters
• Pupil Dilates
• β adrenoreceptors
• Heart Increased rate and force
• Skeletal blood vessels Dilation
• Kidney Renin secretion
• Liver Glycogenolysis
• Bronchi Dilation (via circulating adrenaline)

Receptor transduction (a brief introduction)

• The response of an organ/tissue is dependent on the activation of one of 3 receptor types:
• Muscarinic receptors
• α, β receptors
• Nicotinic receptors
By Duy Thai, 1997 Pharmacology Semester 1 page 4 of 4

• Muscarinic and αβ receptors work via ion channels or second messenger systems, and so they mediate slower
transmission
• Nicotinic receptors are the odd one out.
• They are generally at the site of fast transmission (such as between nerve to nerve, or nerve to skeletal
muscle)

General summary of the effects of the autonomic nervous system

Organ Sympathetic Receptor Parasympathetic Recepotor

Heart Increase rate and force β Decrease rate and force M
Blood vessels
Arteries/veins Constriction α
Skeletal muscle Dilation β
Bronchi
Smooth muscle Dilation (adrenaline) β Constriction M
Glands Secretion M
GIT
Smooth muscle Decrease motility α, β Increase motility M
Sphincters Constriction α Dilation M
Glands Secretion M
Eye
Pupil Dilation α Constriction M
Ciliary muscle Relaxation β Constriction M
Kidney Renin secretion β
Liver Glycogenolysis β
Gluconeogenesis β
Skin
Pilomotor Piloerection α
Sweat glands Secretion (via Ach) M
Adipose tissue Lipolysis β