M&R 10.1/10.2 The ANS Flashcards
The ANS is entirely afferent/efferent but is regulated by afferent/efferent inputs
The ANS is entirely EFFERENT, but is regulated by AFFERENT inputs
Generally in the ANS, are preganglionic fibres myelinated or unmyelinated?
Myelinated
Generally in the ANS, are post-ganglionic fibres myelinated or unmyelinated?
Unmyelinated
Where is the origin of the parasympathetic nerves?
Craniosacral
Lateral horn of medulla (cranial nerves 3,7,9,10)
Sacral region of spinal cord
Describe the preganglionic and post-ganglionic fibres in the PNS, and the location of the ganglia
Preganglionic fibres - Long & myelinated
Ganglia in the tissue innervated by the post-ganglionic fibres
Post-ganglionic fibres - short and unmyelinated
Describe the origin of the sympathetic nerves
Thoracolumbar
From lateral horn of lumbar and thoracic spinal cord
Describe the preganglionic and post-ganglionic fibres in the sympathetic NS and the location of the ganglia
Pre-ganglionic fibres = Short & myelinated
Ganglia - in the paravertebral chain (close to the spinal cord)
Pos-ganglionic fibres = long and unmyelinated
All preganglionic neurons in the ANS use what as their neurotransmitter? What post-ganglionic receptors does it act on?
Acetylcholine
Nicotinic receptors (nAChRs - ligand-gated ion channels)
In the parasympathetic NS, postganglionic neurons release what as their neurotransmitter? What receptors does it act on in the target tissue?
Acetylcholine
Muscarinic receptors (mAChRs - [GPCRs])
In the sympathetic NS, what neurotransmitter do MOST post-ganglionic neurons release? What receptors does it act on in the target tissues?
Noradrenaline (NA)
Adrenoceptors (alpha1, alpha2, beta1, beta2, beta3) - GPCRs
Which post-ganglionic neurones in the sympathetic NS do not release noradrenaline?
What do they release instead? What receptors does it act on?
Those innervating sweat glands and hair follicles (for piloerection)
They release acetylcholine, which acts on muscarinic receptors (mAChRs)
In the sympathetic NS, what are chromaffin cells and what can they be considered as? What do they do?
They are neurosecretory cells in the adrenal glands (adrenal medulla)
They can be considered as post-ganglionic sympathetic neurons that don’t project to a target tissue
Instead they release ADRENALINE into the BLOODSTREAM
In the ANS, what are NANC transmitters? When might they be released?
Non-adrenergic , non-cholinergic transmitters
They can be co-released with either NA or ACh
Name some NANC transmitters found in the ANS
ATP
NO
5-HT (serotonin)
Neuropeptides (e.g. VIP and substance P)
What are the effects of PNS innervation on the heart?
Via which receptors?
Negative choronotropy (bradycardia)
Via ACh acting on M2 receptors in the SAN (and in AVN -to reduce conduction velocity)
What are the effects of PNS innervation on the bronchioles?
Via which receptors?
Bronchoconstriction
Via ACh acting at M3 receptors in lungs
What is the effect of PNS stimulation on the GIT?
Via which receptors?
Increased intestinal motility/secretion
Via ACh acting at M3 receptors in the GIT
Generally, where are M1 receptors found and what are their main effects?
Neural tissue - autonomic ganglia and cerebral cortex (cause CNS excitation)
(some glands)
Generally, where are M2 receptors found and what are their main effects?
Cardiac tissue
- atria of heart (cardiac inhibition - negative chronotropy)
(also in CNS)
Generally, where are M3 receptors found and what are their main effects?
Glandular tissue/smooth muscle
E.g. Exocrine glands (gastric, salivary etc) - increase secretions Smooth muscle (e.g. GIT, eye, airways, bladder) - constriction Blood vessels (endothelium) - vasodilation
Generally, where are alpha1 adrenoceptors found and what are their main effects?
Smooth muscle
- > Blood vessels & bronchi - CONSTRICTION
- > GIT smooth muscle - RELAXATION
- > GI sphincters, uterus, bladder sphincter, seminal tract, radial muscle of iris- CONTRACT
Liver - glycogenolysis
Generally, where are alpha2 adrenoceptors found and what are their main effects?
Pancreatic islets - decrease insulin secretion
Blood vessel SM - constrict/dilate
GIT SM - relax
Generally, where are beta1 adrenoceptors found and what are their main effects?
Heart
- > Increase HR (positive chronotropy)
- > increase force of contraction (positive inotropy)
Generally, where are beta2 adrenoceptors found and what are their main effects?
Smooth muscle
- > blood vessels & bronchi - DILATE
- > GIT, uterus, bladder detrusor, seminal tract & ciliary muscle - RELAX
Skeletal muscle
- > increased muscle mass & speed of contraction
- > glycogenolysis
Liver - glycogenolysis
Generally where are beta3 adrenoceptors found and what do they do?
Skeletal muscle - thermogenesis
Fat - lipolysis, thermogenesis
What do sensory inputs to the ANS do?
Monitor:
Levels of CO2, O2 & nutrients in blood
Arterial pressure
GIT content & chemical composition
Where do the primary sensory neurons of the ANS project? What does this form?
onto ‘second order’ sensory neurons in the medulla oblongata
Forms the nucleus tractus solitarius (nTS) that integrates all visceral afferent information
What are the main steps in neurotransmission (from nerve terminal to receptor)?
- Uptake of precursors 2. Synthesis of NT
- Vesicular storage of NT 4. Degradation of NT (in terminal)
- Depolarisation by AP 6. Influx of Ca2+
- Exocytosis of NT 8. Diffusion of NT across cleft
- Interaction with post-S receptors 10. Inactivation of transmitter
- Reuptake of transmitter 12. Interaction with pre-S receptors
Which steps in neurotransmission are the most common sites of drug action?
- Degradation of NT (in terminal)
- Interaction with post-synaptic receptors
- Inactivation of NT
- Reuptake of NT
- Interaction with pre-synaptic receptors
How is acetylcholine synthesised? What catalyses this?
Acetyl CoA + choline –> acetylcholine + CoA
Catalysed by CAT (cholineacetyltransferase)
How is acetylcholine degraded? What catalyses this?
Acetylcholine –> acetate + choline
Catalysed by AChE (acetylcholinesterase)
How can AChE inhibitors be useful?
By enhancing the actions of endogenously released ACh
E.g. pyrostigmine used for myesthenia gravis
What is the problem with non-selective mAChR agonists?
How might this be prevented?
They will cause autonomic side effects, e.g. decreased heart rate (and therefore decreased CO) , increased bronchoconstriction and GIT peristalsis, increased sweating & salivation
Can be prevented by administering locally - e.g. pilocarpine in glaucoma
What happens after NA is exocytosed (Ca2+ dependent) from the synaptic cleft?
It diffuses across the cleft and acts on adrenoceptors on the post-synaptic membrane
It also interacts with pre-synaptic adrenoceptors to regulate nerve terminal processes (e.g. NT release)
It is rapidly removed from the cleft by transporter proteins (so only has a limited time to influence receptors)
Describe the two processes involved in termination of NA signalling
Uptake 1 - NA actions terminated by reuptake into the terminal by an Na+ dependent, high affinity transporter
Uptake 2 - any NA not captures by uptake 1 is taken up by a lower affinity, non-neuronal mechanism
Which 2 enzymes can metabolise NA that is within the pre-synaptic terminals (not inside vesicles)?
MAO (monoamine oxidase)
COMT
How can exocytosis of NA be modulated?
Pre-synaptic alpha2-adrenoceptor activation
The G-protein beta-gamma subunit can inhibit VGCCs to reduce Ca2+ influx and therefore reduce NT release
How do indirectly acting sympathomimetic agents work in the SNS? What is an example?
They are taken up into noradrenergic synapse vesicles
They cause NA to be displaced from vesicles - it can then leak into the cleft
e.g. amphetamines
Name some drugs that inhibit uptake 1 of NA into the nerve terminal
Tricyclic antidepressants (e.g. amitriptyline) Selective NA reuptake inhibitors e.g. reboxitine
How are beta2 agonists used in asthma?
E.g. salbutamol
Used to revers/oppose bronchoconstriction
Beta2 selectivity important to prevent CVS side effects (positive chronotropy and inotropy via beta1 receptors)
How are beta1 antagonists used in hypertension? What are they otherwise known as?
Decrease heart rate and force of contraction
Beta blockers (e.g. atenolol, bisoprolol)
