MnR S6.5 - Workbook exercise

Question 1

What is acetylcholine synthesised from and which enzyme catalyses this reaction?

Answer 1

Choline and acetate by choline acetyl transferase

Question 2

How is acetylcholine packaged for release?

Answer 2

• Packaged into vesicles using vesicular acetylcholine transporter (VAT)
• Antiport system whereby ACh moves into the protonated vesicles and protons move out

Question 3

Give an example of an agent that interferes with the release of acetylcholine

Answer 3

Botulinum toxins

Cleave the SNARE proteins needed for vesicle to fuse to the synaptic membrane to release ACh

Question 4

How is acetylcholine broken down an what happens to the break down products?

Answer 4

Acetylcholinesterase

Breaks down ACh to acetate which disperses and choline which is reabsorbed by the high affinity choline transport system

Question 5

How do the two main types of acetylcholine receptor differ?

Answer 5

Nicotinic - Ligand gated ion channels

Muscarinic - G-protein coupled receptors

Question 6

What are the effects of acetylcholine on the bronchi, bladder and glands and what receptor does it bind to?

Answer 6

• M3
• Bronchoconstriction
• Contraction in the bladder
• Secretion from glands

Question 7

List two uses of muscarinic antagonists clinically?

Answer 7

• Treatment of GI disorders
• Premedication for general anaesthesia
• Anti-parkinsonian drugs
• Asthma/COPD

Question 8

Define Glaucoma and list some potential causes?

Answer 8

Increased aqueous humour production in the eye results in increased intraocular pressure which decreases blood flow to retinal cells and the optic nerve which can cause blindness

Question 9

Outline the differences in the effects of increasing parasympathetic and sympathetic tone to the eye?

Answer 9

Parasympathetic - Increases outflow of aqueous humour by contraction of the ciliary body; decreases pressure

Sympathetic - Increases aqueous humour production by the ciliary body, increasing pressure and causing dilation of the pupils

Question 10

What agents, active at adrenoceptors, are used in the treatment of glaucoma?

Answer 10

Alpha 2 adrenergic agonist - Brimonidine tartrate

Beta 1 antagonist - Betaxolol

Question 11

List the biogenic amines

Answer 11

• Dopamine
• Noradrenaline
• Adrenaline

Question 12

Outline the steps of noradrenaline synthesis and the enzymes that catalyse each step

Answer 12

• Tyrosine is converted to dopa by tyrosine hydroxylase
• Dopa is converted to dopamine by dopamine decarboxylase
• Dopamine is then covered within the vesicles to noradrenaline by dopamine-beta-hydroxylase

Question 13

How is noradrenaline packaged for release?

Answer 13

• Via Vesicular monoamine transmitter (VMAT)

- Facilitated by the V-ATPase which pumps protons into vesicles creating a proton gradient

Question 14

List the adrenoceptors subtypes and the G protein associated with each receptor

Answer 14

Alpha 1 - Gq

Alpha 2 - Gi

Beta 1 - Gs

Beta 2 - Gs

Question 15

How is noradrenaline removed from the synaptic cleft and what is its fate?

Answer 15

• Reuptake into pre-synaptic axon by noradrenaline transporter
• Symport transporter which takes up noradrenaline with Na+ and Cl-
• Noradrenaline is then either repackaged or broken down

Question 16

What are the two enzymes responsible for the breakdown of noradrenaline?

Answer 16

Catechol-O-methyl transferase

Monoamine oxidase

Question 17

Which product of noradrenaline metabolism can be measured in the blood or urine as an index of sympathetic activity?

Answer 17

Vanillylmandelic acid

Question 18

How does adrenaline assist the actions of noradrenaline in the heart, liver, adipose and skeletal muscle?

Answer 18

Heart - Increases heart rate

Liver - Stimulates lipolysis

Adipose - Stimulates lipolysis

SKM - Stimulate glycogenolysis, vasodilation of blood vessels

Question 19

What is the function of ephedrine and what receptors does it bind to?

Answer 19

• Decongestion of nasal passages

- Alpha and beta adrenoceptors (agonist)

Question 20

What drug is used clinically to prolong the action of local anaesthetic?

Answer 20

Adrenaline

Question 21

How does alpha-methyl tyrosine inhibit noradrenaline release and what can it be used to treat?

Answer 21

• Inhibits enzyme tyrosine hydroxylase so no tyrosine is converted to L-DOPA so no noradrenaline in produced
• Pheochromocytoma (an adrenal tumour causing irregular secretion of adrenaline and noradrenaline)

Question 22

How does alpha-methyl DOPA inhibit noradrenaline release and what is produced instead?

Answer 22

• Acts as a false substrate for DOPA decarboxylase

- No DOPA is converted to dopamine and alpha-methyl noradrenaline is produced instead

Question 23

Name a molecule other that alpha-methyl DOPA and alpha-methyl tyrosine that blocks noradrenaline release and outline how it does this

Answer 23

• Guanethidine

- Can cross synaptic nerve membrane and behaves like noradrenaline so is packaged into vesicles instead of noradrenaline

Question 24

Why is guanethidine no longer used clinically?

Answer 24

Unwanted side effects such as swelling, chest pain, dizziness and diarrhoea