Autonomic Pharmacology 1
Jason Waechter MD
Nov/2006
Objectives:
• ultra brief overview of the autonomic nervous system (ANS)
o anatomical arrangement
o ganglia and ganglionic neurotransmitters
o receptor types, receptor distribution, and receptor function
• describe general principles how to manipulate the ANS
• provide a scheme to help remember SNS and PNS
Introduction
• The autonomic nervous system functions independently of the conscious
nervous system (for example, you do not need to consciously tell your heart to
beat faster when you exercise). However, the ANS can be influenced by the brain
(for example, Pavlov’s dog salivating at the sound of a bell).
• the autonomic nervous system has 2 parts:
o sympathetic nervous system (SNS)
o parasympathetic nervous system (PNS)
• the SNS is the “Fight or Flight” response
• the PNS usually causes the opposite effect to that of the SNS
• anatomical arrangement of the ANS is well described in Boron pg. 382
Autonomic Anatomy:
• Parasympathetic nerves are arranged in a “craniosacral” distribution:
o they follow cranial nerves: III, VII, IX and X (X = Vagus)
o they follow splanchnic nerves which arise from sacral nerves
• The sympathetic nerves primarily arise from the thoracic and lumbar spine.
• Therefore, the parasympathetics are anatomically originate from the top and
bottom of the CNS and the sympathetics are “in the middle”.
Ganglia and Neurotransmitters:
• For both the sympathetic and parasympathetic systems, the nerves exit the brain
or spinal cord and then enter a “relay station” called a ganglion.
• Not much occurs except for the transfer of the signal from the “presynaptic”
neuron to the “postsynaptic” neuron. The neurotransmitter for both the SNS and
PNS ganglia is acetylcholine.
• The postsynaptic neuron then connects to an organ. If this neuron is a sympathetic
neuron, then the neurotransmitter will be norepinephrine. If this neuron is a
parasympathetic neuron, then the neurotransmitter will be acetylcholine.
• The parasympathetic ganglia are located close to the organs that they innervate.
• This is in contrast to sympathetic ganglia which are located in the sympathetic
chain which runs alongside the spinal column and are far away from the organs.
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Ganglia and Neurotransmitters:
• Acetylcholine (Ach) is the “preganglionic nerve to postganglionic nerve”
transmitter in the ganglia for both the sympathetic and parasympathetic systems.
• Acetylcholine is the “postganglionic nerve to organ” neurotransmitter for the
parasympathetic system and (norepinephrine (NE) is the transmitter for the
sympathetic system).
Ganglion (near organ)
Spinal
Cord
or
Brain
Ach
Ach
Parasympathetic
Target Organ
Ach
NE
Sympathetic
Ganglion
(Sympathetic chain)
Special case: the sympathetic innervation of the adrenal gland is direct from the spinal
cord and uses Ach as the neurotransmitter. The adrenal gland functions like a special
form of ganglion which secretes epinephrine directly into the bloodstream. (Boron p. 386)
Autonomic Receptors:
• Acetylcholine binds to muscarinic and nicotinic receptors, abbreviated M and N
o N receptors are in ANS ganglia and also in “nerve to muscle” connections
(the neuromuscular junction)
o M receptors are on organs which receive parasympathetic innervation
• Norepinephrine (and epinephrine also) bind to alpha and beta receptors (α and β)
• Subtypes for these receptors exist, such as M1, M2, M3 and α1, α2, β1, β2. There are
even more subtype classifications that exist.
• The subtypes that you must know are: α1, α2, β1, and β2. You must know the
distribution and function of these receptors in the body (next page).
• FYI, autonomic receptors also exist in many parts of the body but function in nonautonomic processes. Some examples include:
o nicotine receptors in the addiction pathway
o nicotine receptors in the neuromuscular junction, mediating skeletal
muscle innervation
muscarinic receptors in the brain involved in Parkinson’s disease and related
movement disorders
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Autonomic Receptors: Function and Distribution
Sympathetic Receptors:
α1
•
•
function: constriction of smooth muscles
distribution:
blood vessels and piloerectors in skin (vasoconstriction and goosebumps)
sphincters (bladder, GI)
uterus (contraction)
eye (contraction of the radial muscle = pupilary dilation/mydriasis)
•
•
function: inhibition of sympathetic autonomic ganglia (decreases the SNS)
distribution:
pre-synaptic ganglionic neurons
GI tract (less important pharmacologically, included for completeness)
•
•
function: increase cardiac performance and liberation of energy
distribution:
heart (the most important for β1)
fat cells (release fat for energy via lipolysis)
kidney (release renin to conserve water)
•
•
function: relaxation of smooth muscles and liberation of energy
distribution:
lungs (bronchodilation)
blood vessels in muscles (vasodilation)
uterus (uterine relaxation)
GI (intestinal relaxation)
bladder (bladder relaxation)
liver (to liberate glucose via glycogenolysis)
α2
β1
β2
Parasympathetic Receptors
N (nicotinic)
• function: “nerve to nerve” and “nerve to muscle” communication
• distribution:
sympathetic and parasympathetic ganglia
neuromuscular junction (NMJ)
M (muscarinic)
• function: to oppose most sympathetic actions at the level of the organs
• distribution:
lung (bronchoconstriction)
heart (slower rate, decreased conduction, decreased contractility)
sphincters of GI and bladder (relax)
bladder (constriction)
GI (intestinal contraction)
eye (contraction of the circular muscle = pupilary constriction/meiosis)
eye (contraction of the ciliary muscle = focus for near vision)
glands: lacrimal, salivary, bronchial (secretion)
Special notes:
• There is no parasympathetic innervation of blood vessels.
• Sweat glands are innervated by sympathetic nerves, but paradoxically use M receptors.
• Sexual arousal is parasympathetic but orgasm is sympathetic.
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Manipulating the ANS:
There are 2 systems: the SNS and the PNS. Most of the time, each system is opposing the
other. Therefore, to change this balance, we can strengthen one system or weaken the
other:
• ↑ Sympathetic:
o you want to increase stimulation of the α and β receptors:
o give an agonist (sympathomimetic) that stimulates these receptors
o inhibit the breakdown or removal of endogenous (the body’s own)
norepinephrine or epinephrine
• ↓ Sympathetic:
o you want to decrease stimulation of the α and β receptors:
o give an antagonist (sympatholytic) that blocks these receptors
o give a drug to “turn down” the ganglion (relay station)
• ↑ Parasympathetic:
o you want to increase stimulation of the M receptors
o give an agonist (vagotonic) (Vagus nerve = primary PNS nerve)
o inhibit the breakdown or removal of endogenous acetylcholine
• ↓ Parasympathetic:
o decrease M receptor stimulation
o give an antagonist (vagolytic)
Predicting the Sympathetic Response (Fight or Flight)
Organ
Eye
Salivary Glands
Airways
Gut/Digestion
Pancreas/Liver (glucose metabolism)
Heart rate
Heart contraction strength
Heart conduction speed
Bladder wall
Bladder sphincter
Sweat Glands
Response
References:
Medical Physiology, Boron, Ch 15 “The Autonomic Nervous System”.
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