M&R 10.1/10.2 The ANS

Question 1

The ANS is entirely afferent/efferent but is regulated by afferent/efferent inputs

Answer 1

The ANS is entirely EFFERENT, but is regulated by AFFERENT inputs

Question 2

Generally in the ANS, are preganglionic fibres myelinated or unmyelinated?

Answer 2

Myelinated

Question 3

Generally in the ANS, are post-ganglionic fibres myelinated or unmyelinated?

Answer 3

Unmyelinated

Question 4

Where is the origin of the parasympathetic nerves?

Answer 4

Craniosacral

Lateral horn of medulla (cranial nerves 3,7,9,10)
Sacral region of spinal cord

Question 5

Describe the preganglionic and post-ganglionic fibres in the PNS, and the location of the ganglia

Answer 5

Preganglionic fibres - Long & myelinated

Ganglia in the tissue innervated by the post-ganglionic fibres

Post-ganglionic fibres - short and unmyelinated

Question 6

Describe the origin of the sympathetic nerves

Answer 6

Thoracolumbar

From lateral horn of lumbar and thoracic spinal cord

Question 7

Describe the preganglionic and post-ganglionic fibres in the sympathetic NS and the location of the ganglia

Answer 7

Pre-ganglionic fibres = Short & myelinated

Ganglia - in the paravertebral chain (close to the spinal cord)

Pos-ganglionic fibres = long and unmyelinated

Question 8

All preganglionic neurons in the ANS use what as their neurotransmitter? What post-ganglionic receptors does it act on?

Answer 8

Acetylcholine

Nicotinic receptors (nAChRs - ligand-gated ion channels)

Question 9

In the parasympathetic NS, postganglionic neurons release what as their neurotransmitter? What receptors does it act on in the target tissue?

Answer 9

Acetylcholine

Muscarinic receptors (mAChRs - [GPCRs])

Question 10

In the sympathetic NS, what neurotransmitter do MOST post-ganglionic neurons release? What receptors does it act on in the target tissues?

Answer 10

Noradrenaline (NA)

Adrenoceptors (alpha1, alpha2, beta1, beta2, beta3) - GPCRs

Question 11

Which post-ganglionic neurones in the sympathetic NS do not release noradrenaline?
What do they release instead? What receptors does it act on?

Answer 11

Those innervating sweat glands and hair follicles (for piloerection)

They release acetylcholine, which acts on muscarinic receptors (mAChRs)

Question 12

In the sympathetic NS, what are chromaffin cells and what can they be considered as? What do they do?

Answer 12

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

Question 13

In the ANS, what are NANC transmitters? When might they be released?

Answer 13

Non-adrenergic , non-cholinergic transmitters

They can be co-released with either NA or ACh

Question 14

Name some NANC transmitters found in the ANS

Answer 14

ATP
NO
5-HT (serotonin)
Neuropeptides (e.g. VIP and substance P)

Question 15

What are the effects of PNS innervation on the heart?

Via which receptors?

Answer 15

Negative choronotropy (bradycardia)

Via ACh acting on M2 receptors in the SAN (and in AVN -to reduce conduction velocity)

Question 16

What are the effects of PNS innervation on the bronchioles?

Via which receptors?

Answer 16

Bronchoconstriction

Via ACh acting at M3 receptors in lungs

Question 17

What is the effect of PNS stimulation on the GIT?

Via which receptors?

Answer 17

Increased intestinal motility/secretion

Via ACh acting at M3 receptors in the GIT

Question 18

Generally, where are M1 receptors found and what are their main effects?

Answer 18

Neural tissue - autonomic ganglia and cerebral cortex (cause CNS excitation)

(some glands)

Question 19

Generally, where are M2 receptors found and what are their main effects?

Answer 19

Cardiac tissue
- atria of heart (cardiac inhibition - negative chronotropy)

(also in CNS)

Question 20

Generally, where are M3 receptors found and what are their main effects?

Answer 20

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

Question 21

Generally, where are alpha1 adrenoceptors found and what are their main effects?

Answer 21

Smooth muscle

• > Blood vessels & bronchi - CONSTRICTION
• > GIT smooth muscle - RELAXATION
• > GI sphincters, uterus, bladder sphincter, seminal tract, radial muscle of iris- CONTRACT

Liver - glycogenolysis

Question 22

Generally, where are alpha2 adrenoceptors found and what are their main effects?

Answer 22

Pancreatic islets - decrease insulin secretion

Blood vessel SM - constrict/dilate
GIT SM - relax

Question 23

Generally, where are beta1 adrenoceptors found and what are their main effects?

Answer 23

Heart

• > Increase HR (positive chronotropy)
• > increase force of contraction (positive inotropy)

Question 24

Generally, where are beta2 adrenoceptors found and what are their main effects?

Answer 24

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

Question 25

Generally where are beta3 adrenoceptors found and what do they do?

Answer 25

Skeletal muscle - thermogenesis Fat - lipolysis, thermogenesis

Question 26

What do sensory inputs to the ANS do?

Answer 26

Monitor: Levels of CO2, O2 & nutrients in blood Arterial pressure GIT content & chemical composition

Question 27

Where do the primary sensory neurons of the ANS project? What does this form?

Answer 27

onto 'second order' sensory neurons in the medulla oblongata Forms the nucleus tractus solitarius (nTS) that integrates all visceral afferent information

Question 28

What are the main steps in neurotransmission (from nerve terminal to receptor)?

Answer 28

1. Uptake of precursors 2. Synthesis of NT 3. Vesicular storage of NT 4. Degradation of NT (in terminal) 5. Depolarisation by AP 6. Influx of Ca2+ 7. Exocytosis of NT 8. Diffusion of NT across cleft 9. Interaction with post-S receptors 10. Inactivation of transmitter 11. Reuptake of transmitter 12. Interaction with pre-S receptors

Question 29

Which steps in neurotransmission are the most common sites of drug action?

Answer 29

4. Degradation of NT (in terminal) 9. Interaction with post-synaptic receptors 10. Inactivation of NT 11. Reuptake of NT 12. Interaction with pre-synaptic receptors

Question 30

How is acetylcholine synthesised? What catalyses this?

Answer 30

Acetyl CoA + choline --> acetylcholine + CoA Catalysed by CAT (cholineacetyltransferase)

Question 31

How is acetylcholine degraded? What catalyses this?

Answer 31

Acetylcholine --> acetate + choline Catalysed by AChE (acetylcholinesterase)

Question 32

How can AChE inhibitors be useful?

Answer 32

By enhancing the actions of endogenously released ACh E.g. pyrostigmine used for myesthenia gravis

Question 33

What is the problem with non-selective mAChR agonists? | How might this be prevented?

Answer 33

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

Question 34

What happens after NA is exocytosed (Ca2+ dependent) from the synaptic cleft?

Answer 34

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)

Question 35

Describe the two processes involved in termination of NA signalling

Answer 35

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

Question 36

Which 2 enzymes can metabolise NA that is within the pre-synaptic terminals (not inside vesicles)?

Answer 36

MAO (monoamine oxidase) | COMT

Question 37

How can exocytosis of NA be modulated?

Answer 37

Pre-synaptic alpha2-adrenoceptor activation | The G-protein beta-gamma subunit can inhibit VGCCs to reduce Ca2+ influx and therefore reduce NT release

Question 38

How do indirectly acting sympathomimetic agents work in the SNS? What is an example?

Answer 38

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

Question 39

Name some drugs that inhibit uptake 1 of NA into the nerve terminal

Answer 39

``` Tricyclic antidepressants (e.g. amitriptyline) Selective NA reuptake inhibitors e.g. reboxitine ```

Question 40

How are beta2 agonists used in asthma?

Answer 40

E.g. salbutamol Used to revers/oppose bronchoconstriction Beta2 selectivity important to prevent CVS side effects (positive chronotropy and inotropy via beta1 receptors)

Question 41

How are beta1 antagonists used in hypertension? What are they otherwise known as?

Answer 41

Decrease heart rate and force of contraction Beta blockers (e.g. atenolol, bisoprolol)