Week 10 - ANS

Question 1

Which transmitters are found in the ANS?

Answer 1

Mainly: acetylcholine and noradrenaline
- ATP
- Nitric oxide
- 5-hydroxytryptamine
- Neuropeptides
These may be released with either NA or ACh

Question 2

Describe sympathetic neurones in the adrenal glands

Answer 2

• They differentiate to form neurosecretory chromatin cells
• – Can be considered as postganglionic sympathetic neurons that do not project to a target tissue
• These cells release adrenaline into the bloodstream upon sympathetic stimulation

Question 3

How is acetylcholine synthesised?

Answer 3

Acetyl CoA + choline –> ACh + CoA

- Enzyme = choline acetyl-transferase

Question 4

How is acetylcholine degraded?

Answer 4

Acetylcholine –> acetate + choline

- Enzyme = acetylcholesterase

Question 5

Where is acetylcholine stored?

Answer 5

Synaptic vesicles

Question 6

How is noradrenaline synthesised?

Answer 6

• Tyrosine –> DOPA (via tyrosine hydroxylase)
• DOPA –> dopamine (via DOPA decarboxylase)
• Dopamine –> noradrenaline (via dopamine ß-hydroxylase)

Question 7

How does degradation of noradrenaline occur?

Answer 7

Termination:
- Uptake 1: NA actions are terminated by re-uptake into the presynaptic terminal by a Na+ dependent, high affinity transporter
- Uptake 2: NA not captured by uptake 1 is taken up by a lower affinity, non-neuronal mechanism
Metabolism:
- Within the pre-synaptic terminal, NA not taken up into vesicles is susceptible to metabolism by 2 enzymes (monoamine oxidase, catechol-O-methyltransferase

Question 8

How does noradrenaline act?

Answer 8

• Released by Ca2+ mediated endocytosis
• Released NA can interact with both pre- and post-synaptic adrenoceptors
• But the opportunity to interact with receptors is limited by a high affinity re-uptake system

Question 9

What are some drugs that affect cholinergic transmission and what do they do?

Answer 9

• Nicotinic cholinoceptor antagonist (e.g. Tubocurarine) = muscle paralysis during anaesthesia
• Muscarinic cholinoceptor agonist (e.g. Pilocarpine = treatment of glaucoma, bethanechol = bladder emptying)
• Muscarinic cholinoceptor antagonist (e.g. Ipratropium + tiotropium = treatment of some forms of asthma and COPD, tolterodine, darifenain + oxybutynin = to treat overactive bladder)
• Cholesterase inhibitors (e.g. Pyridostigmine = to treat myasthenia gravis, bonepezil = to treat alzheimers)
• Ganglion blockers (e.g. Trimethaphan = used in hypertensive emergencies and to produce controlled hypotension during surgery)

Question 10

What are the main drug types that act on adrenergic receptors?

Answer 10

• Selective β1 agonist (e.g. Dobutamine)
• Selective β2 agonist (e.g. Salbutamol)
• Selective α1 agonist (e.g. Phenylephrine, adrenaline)
• Selective α2 agonist (e.g. Clonidine)
• α-antagonist (e.g. phentolamine)
• Selective α1 antagonist (e.g. Prazosin)
• β-antagonist (e.g. Propranolol)

Question 11

What are the main drug types that act on adrenergic nerve terminals and how do they act?

Answer 11

• Indirectly acting sympathomimetic agents: taken up into NA synaptic vesicles, cause NA to leak out into synaptic cleft
• Uptake 1 inhibitors: exert main therapeutic action in the CNS, peripheral actions are unwanted side effects

Question 12

What is tachyphylaxis?

Answer 12

Excessive exposure to an agonist which has lead to reduced sensitivity