Acetylcholine

Question 1

Where in the parasympathetic nervous system is acetylcholine found?

Answer 1

In both pre and postganglionic synapses

Question 2

Where in the sympathetic nervous system is acetylcholine found?

Answer 2

In preganglionic fibres and at neuroeffector junctions for arrector pili muscles and thermoregulatory sweat glands.

Question 3

What are the precursors for acetylcholine and what enzyme converts them to it?

Answer 3

Acetate and choline.

Choline acetyl transferase (ChAT)

Question 4

Where in a neuron is acetylcholine produced?

Answer 4

Presynaptic bulb

Question 5

Where do the precursors for acetylcholine come from?

Answer 5

Acetate from acetyl~CoA

Choline taken up by CHT closer to the synapse

Question 6

How is acetylcholine packaged into vesicles?

Answer 6

V-AChT

Question 7

Describe the regulation of acetylcholine release.

Answer 7

Synaptotagmin is bound to the vesicle and attaches to a SNARE complex (VAMPs and SNAPs).
When calcium ions enter the bulb it causes the complex to open and form a fusion pore.

Question 8

Describe one substance which prevents the release of acetylcholine.

Answer 8

Botulism toxin - cleaves the SNARE proteins to prevent the complex from forming

k-neurotoxin - stops the fusion pore opening

Question 9

Describe how acetylcholine action is terminated

Answer 9

Acetylcholinesterase breaks down ACh in the synapse.

Question 10

What drugs prevent the termination of acetylcholine action and what can they be used for?

Answer 10

Neostigmine/pyridostigmine

Reverse neuromuscular block or treat myasthenia gravis

Question 11

Describe the fate of the products of acetylcholine breakdown

Answer 11

Free choline taken up by a high affinity choline uptake system and is only used to make ACh.
Acetate disperses freely into the surrounding tissues and can be used to make acetyl~CoA

Question 12

What type of receptors are nicotinic cholinoceptors?

Answer 12

Ligand gated ion channels which are permeable to both sodium and potassium

Question 13

What type of receptor are muscarinic cholinoceptors?

Answer 13

G-protein coupled receptors.

Question 14

Give the four subtypes of muscarinic cholinoceptors and their action.

Answer 14

M1 - Gq - activate phospholipase C
M2 - Gi - inhibit adenylyl cyclase
M3 - Gq - activate phospholipase C
M4 - Gi - inhibit adenylyl cyclase

Question 15

What type of muscarinic cholinoceptor is found in the SAN and what action does it have?

Answer 15

M2

Decreases cAMP which reduces HCN channel activation and therefore decreases heart rate

Question 16

What type of muscarinic cholinoceptor is found in the bronchi and what action does it have?

Answer 16

M3

Increases intracellular calcium which increases contraction

Question 17

What type of muscarinic cholinoceptor is found in the bladder and what action does it have?

Answer 17

M3

Dilates the bladder by reducing smooth muscle contraction

Question 18

What type of muscarinic cholinoceptor is found in exocrine glands and what action does it have?

Answer 18

M1

Increases function by increasing cAMP

Question 19

What type of muscarinic cholinoceptor is found in salivary glands and what action does it have?

Answer 19

M3

Increases calcium and fluid secretion

Question 20

What type of muscarinic cholinoceptor is found in PNS terminals and what action does it have?

Answer 20

M1

Decreases potassium conductance

Question 21

What is the advantage of synthesising cholinoceptor agonists which are specific for a receptor subtype?

Answer 21

Decreases the number and severity of side effects.

Question 22

Give the effect of parasympathetic action on one area of the eye.

Answer 22

Contract sphincter pupillae which constricts the pupil

Contracts ciliary muscle which focusses the eye for near vision

Enhance drainage of aqueous humour through the trabecular meshwork or canal of Schlemm

Question 23

Give the effect of sympathetic action on one area of the eye.

Answer 23

Contracts dilator pupillae which dilates the pupil

Contracts the superior tarsal muscle in the eyelid to help to hold it open.

Enhances aqueous humour formation (beta-2)

Inhibits aqueous humour formation (alpha-1)

Relaxes ciliary muscle for distant vision

Question 24

Describe what causes glaucoma.

Answer 24

Reduced ability to drain fluid out of the eye due to blocked trabecular meshwork.
Can be caused by diabetic retinopathy, prolonged steroid use and trauma.

Question 25

Describe a treatment for glaucoma.

Answer 25

Pilocarpine which activates M3 receptors

Alpha adrenergic agonists which decreases production of aqueous humour by ciliary bodies and increases uveoscleral flow

Prostaglandin analogues as the receptors increase outflow of fluid

Beta adrenergic antagonists which decrease aqueous humour production

Acetylcholinesterase inhibitors which decrease the breakdown of ACh so increase the stimulation of muscarinic receptors

Brimodine which inhibits adenylyl cyclase, reducing cAMP production and causing vasoconstriction. Decreases aqueous humour production and increases uveoscleral outflow