Autonomic Nervous System Flashcards
What does the autonomic nervous system do?
The ANS controls all vegetative (involuntary) functions
Give examples of what is controlled by the ANS?
heart rate - blood pressure - GI motility - iris diameter
What are the two divisions of ANS?
- The sympathetic division
2. The parasympathetic division
What does the sympathetic nervous system respond to and what changes does it bring?
The sympathetic nervous system responds to stressful situations • “fight or flight” response • heart rate increases • force of contraction increases • blood pressure increases
What does the parasympathetic nervous system control?
The parasympathetic nervous system regulates basal
activities (e.g. basal heart rate) - “rest and digest”
Is the ANS efferent or afferent?
It is entirely efferent (but is regulated by afferent inputs)
What are the Anatomical divisions of brain stem and spinal cord?
M = medullary C = cranial T = thoracic L = lumbar S = sacral
Which regions of the spinal cord, does the sympathetic system emerge from?
In the central regions:
Thoracic and lumbar
Which regions of the CNS, does the parasympathetic system emerge from?
The medullary and sacral regions (from the brain stem and lower part of spinal cord)
In both the parasympathetic and sympathetic system, where is the pre-ganglion is cell body found?
In the CNS
In both the parasympathetic and sympathetic system, where is the post-ganglion is cell body found?
In the PNS
In both the sympathetic and parasympathetic system, which neurone is myelinated and which is unmyelinated?
The pre-ganglionic neurone is myelinated and postganglionic neurone is unmyelinated
In the sympathetic system, which neurone is longer?
The post-ganglionic neurone
In the parasympathetic system, which neurone is longer?
The pre-ganglionic neurone
Where do parasympathetic nerves originate from?
Originate in the lateral horn of the medulla [and sacral spinal cord]
Where do sympathetic nerves originate from?
Originate in the lateral horn of the lumbar and thoracic spinal cord
In the parasympathetic nerves, where are the ganglia located?
Ganglia are located within the innervated tissues
In the sympathetic nerves, where are the ganglia located?
Ganglia are located in the paravertebral (sympathetic)chain close to the spinal cord
Which are the principal neurotransmitters in the ANS?
- acetylcholine (ACh)
* noradrenaline (NA) (US name: norepinephrine)
Which neurotransmitter do parasympathetic and sympathetic pre-ganglionic neurones release at the ganglia?
ACh
What does the pre-ganglionic release of ACH result in?
the activation of post-ganglionic nicotinic ACh receptors which results in influx of Na+ ions that causes depolarisation and carries the impulse forward
What type of receptors are Nicotinic ACh receptors?
ligand-gated ion channels
True or false, All pre-ganglionic neurons are cholinergic?
True
What type of neurones are Parasympathetic post-ganglionic neurons ?
Cholinergic
Which receptors do ACh released by Parasympathetic post-ganglionic neurons act on in the target tissue?
muscarinic ACh (mACh) receptors
What type of receptors are muscarinic ACh (mACh) receptors?
mACh receptors are G-protein coupled receptors (GPCRs).
How many types of mACh receptor subtypes are there?
There are five mACh receptor subtypes (M 1,M2,M3,M4,M5).
What type of neurones are most sympathetic post-ganglionic neurons?
Noradrenergic
Which is the principal neurotransmitter released by Most sympathetic post-ganglionic neurons ?
noradrenaline (NA)
What are the subdivisions of the α-adrenoceptors and β-adrenoceptors?
subdivided into α1 and α2 and β1,β2 and β3 subtypes
Which receptors do noradrenaline (NA) interact with?
α-adrenoceptors and β-adrenoceptors
Some specialized sympathetic post-ganglionic neurons are
cholinergic, not noradrenergic. Which are they?
those innervating sweat glands, hair follicles (piloerection)
Can transmitters other than NA and ACh be found in the ANS?if so, what are they?
Yes, Non-Adrenergic, Non-Cholinergic (NANC) transmitters
When are theses other transmitters in the ANS released?
They may be co-released with either NA or ACh
Give examples of Non-Adrenergic, Non-Cholinergic (NANC) transmitters
ATP nitric oxide (NO) 5-hydroxytryptamine (5HT; serotonin) neuropeptides (e.g. VIP (vasoactive intestinal peptide), substance P)
What is the third division of the autonomic nervous system?
The enteric nervous system
What does the enteric nervous system control?
Controls the gastrointestinal system
How are Sympathetic postganglionic neurons in the
adrenal glands different?
• They differentiate to form neurosecretory chromaffin cells
• Chromaffin cells can be considered as postganglionic sympathetic
neurons that do not project to a target tissue
• Instead, on sympathetic stimulation these cells release
adrenaline (US name: epinephrine) into the bloodstream
Where are chromaffin cells found?
Chromaffin cells are present in the
adrenal medulla
What innervates the chromaffin cells?
Chromaffin cells are innervated by pre-ganglionic sympathetic neurons
Which neurotransmitter is used by the somatic efferent system?
Acetylcholine on nicotinic acetylcholine receptors
What is the physiological consequence of parasympathetic release of ACh on the heart? Which receptor does it act on?
Heart(atria):
M2 muscarinic receptors:
- bradycardia - SA node
- reduced cardiac conduction velocity - AV node
What is the physiological consequence of parasympathetic release of ACh on smooth muscle? Which receptor does it act on?
Smooth muscle:
M3 muscarinic receptors:
• bronchial/bronchiolar contraction - lungs
• increased intestinal mobility/secretion - GI tract
• bladder contraction (detrusor) and relaxation (trigone/sphincter)- GU tract
nitric oxide generation:
• penile erection - GU tract
• ciliary muscle and iris sphincter contraction - eye
What is the physiological consequence of parasympathetic release of ACh on glands? Which receptor does it act on?
M1/M1 muscarinic receptors:
• increased sweat/salivary/lacrimal secretion -
What is the physiological consequence of sympathetic release of NA on the heart? Which receptor does it act on?
Heart (atria/ventricles);
B1 adrenoceptors:
• tachycardia (positive chronotropy) - SA node
• positive inotropy - ventricles
What is the physiological consequence of sympathetic release of NA on smooth muscle? Which receptor does it act on?
Smooth muscle:
a1, B2:
• arteriolar contraction/venous contraction
(arteriolar relaxation in some vascular beds) - vascularise
B2:
• bronchiolar/intestinal/uterine relaxation - lungs/GI/GU tract
• bladder sphincter contraction - GU tract
A1:
•radial muscle contraction - eye
What is the physiological consequence of sympathetic release of NA on glands? Which receptor does it act on?
Glandular
• increased (viscous) secretion - salivary
What is the physiological consequence of sympathetic release of NA on the kidney? Which receptor does it act on?
Kidney
A1:
• renin release
What are the basic steps in neurotransmission?
- uptake of precursors
- synthesis of transmitter
- vesicular storage of transmitter
- degradation of transmitter
- depolarization by propagated action potential
- depolarization-dependent influx of Ca2+ 4
- exocytotic release of transmitter
- diffusion to post-synaptic membrane
- interaction with post-synaptic receptors
- inactivation of transmitter
- re-uptake of transmitter
- interaction with pre-synaptic receptors
How is acetylcholine made?
It is made from acetyl coenzyme A and choline by the enzyme choline acetyltransferase
Acetyl CoA + choline —-> acetylcholine + coenzyme A
How is acetylcholine degraded?
Via acetylcholine esterase (AChE)
Acetylcholine —-> acetate + choline
Describe cholinergic transmission
• Choline from diet and acetyl CoA is combined to make acetylcholine
• Th acetylcholine is packaged into vesicles
• Upon depolarisation of the membrane, the vesicle fuses with the presynaptic membrane and releases the acetycholine into the synaptic cleft
• The acetycholine has two fates:
1. The acetylcholine will interact with receptors and pass on the signal
2. Acetylcholine is degraded
How are we able to produce drugs that only target nicotinic acetylcholine receptors in autonomic ganglia?
Nicotinic acetylcholine receptors (nAChRs) at autonomic ganglia and the neuromuscular junction differ in structure.
What are drugs that target Nicotinic acetylcholine receptors (nAChRs) at autonomic ganglia called?
ganglion-blocking drugs
Give an example of a ganglion-blocking drug and when is it used?
trimethaphan, which is used in hypertensive emergencies and to produce controlled hypotension during surgery
Give an example of a mAChR antagonist. What is it used for?
tolterodine, which is used to treat “overactive bladder”
Give two examples of AChE inhibitors which enhance the actions of ACh. What are they used to treat?
- pyridostigmine*, used to treat myasthenia gravis;
* donepezil*, used to treat Alzheimer’s disease
Why are do unwanted side effects often limit the usage of cholinergic drugs?
They have a reletive lack of selectivity
What side effects could a non-selective, muscarinic ACh receptor agonist cause?
Heart rate and cardiac output decreases
In smooth muscle: bronchoconstriction and GI tract peristalsis increases
In exocrine glands: sweating and salivation increases
What is the mnemonic for the pathological effects indicative of massive discharge of the parasympathetic nervous system?
SLUDGE
What does the mnemonic SLUDGE stand for?
Salivation: Stimulation of he salivary glands
Lacrimation: Stimulation of the lacrimal glands-tears
Urination:
Defecation
Gastrointestinal upset:
Emesis: Vomiting
What usually causes SLUDGE?
drug overdose
ingestion of “magic” mushrooms
exposure to organophosphorus insecticides (e.g. parathion),
or nerve gases (e.g. sarin)
What do nerve gases do?
covalently-modify acetylcholinesterase, to irreversibly deactivate the enzyme and raise acetylcholine levels.
What usually causes the symptoms of SLUDGE?
The symptoms of SLUDGE are primarily due to chronic (over-)
stimulation of muscarinic acetylcholine receptors, in organs and
muscles innervated by the parasympathetic nervous system.
How is SLUDGE treated?
SLUDGE may be treated with atropine, pralidoxime, or other anti-cholinergic agents. They are antagonists of muscarinic acetylcholine receptors.
When is it useful to use mACh receptor agonists and antagonists?
when they can be administered locally, rather than systemically.
Give two examples of Muscarinic ACh receptor agonists and what they are used for
pilocarpine and bethanechol are respectively used to treat glaucoma and acutely to stimulate bladder emptying.
Why are there few side effects of using pilocarpine to treat glaucoma?
It can be administered as eye drops so act locally not systemically
Give examples of Muscarinic ACh receptor antagonists
ipratropium and tiotropium are used to treat some forms of asthma and chronic obstructive pulmonary disease (COPD).
Tolterodine , darifenacin and oxybutynin are used to treat overactive bladder.
Describe Post-ganglionic sympathetic neurons
Post-ganglionic sympathetic neurons generally possess a highly branching axonal network with numerous varicosities, each of which is a specialized site for Ca2+-dependent noradrenaline release.
Describe noradrenaline synthesis
- Tryosine is obtained form the diet
- Tyrosine is an amino acid that is taken up by the varicosity and conveyed to an intermediate called DOPA
- The DOPA is converted to dopamine
- Dopamine is taken up by vesicles that are lined by an enzyme called dopamine B-hydroxylase that convert all of what is taken up into noradrenaline
Within the adrenal medulla noradrenaline is converted to adrenaline by the enzyme (phenylethanolamine N- methyltransferase)
What happens following Ca2+-dependent exocytotic release of NA?
• NA diffuses across the synaptic cleft and interacts with
adrenoceptors in the post-synaptic membrane to initiate
signalling in the effector tissue
• NA interacts with pre-synaptic adrenoceptors to regulate
processes within the nerve terminal - e.g. NA release
Why does noradrenaline only have a very limited time in which to influence pre-
and post-synaptic adrenoceptors?
NA has only a very limited time in which to influence pre-and post-synaptic adrenoceptors as it rapidly removed from the synaptic cleft by noradrenaline transporter proteins
What happens during (Nor)adrenergic transmission ?
• NA actions are terminated by re-uptake into the pre-synaptic
terminal by a Na+-dependent, high affinity transporter
‘Uptake 1’
• NA not re-captured by Uptake 1 is taken up by a lower
affinity, non-neuronal mechanism
‘Uptake 2’
Which two enzymes metabolise the noradrenaline within the pre-synaptic terminal that are not taken up into vesicles?
- monoamine oxidase (MAO)
* catechol-O-methyltransferase (COMT)
Where in noradrenergic transmission can drugs interfere?
In the noradrenaline synthesis
Packaging of noradrenaline
Receptor processes
Reuptake systems
What types of drugs are used clinically to target receptors?
Subtype-selective adrenoceptor agonists and antagonists are used clinically
Give an example of an agonist that is used to target receptors in noradrenergic transmission and what it is used for
β-adrenoceptor-selective agonists (e.g. salbutamol) are used
in asthma to reverse/oppose bronchoconstriction
Why is β 2-adrenoceptor-selectivity of such agents important?
The β 2
-adrenoceptor-selectivity of such agents is
important as it limits possible cardiovascular side-effects (e.g. positive inotropic and positive chronotropic actions)
Give an example of an antagonist that is u
α1-adrenoceptor-selective antagonists (e.g. doxazosin) and β 1-adrenoceptor-selective antagonists (e.g. atenolol)
are used to treat a number of cardiovascular disorders, including hypertension.
