ELM 2.1

Question 1

How many subtypes of muscarinic receptors are there?

Answer 1

5

Question 2

Choline acetyltransferase is located:

Answer 2

In the cytoplasm

Question 3

Presynaptic nerve terminals have specific transporters for__________ in their membranes.

Answer 3

choline

Question 4

Where are nicotinic acetylcholine receptors found? (3)

Answer 4

• skeletal neuromuscular junction
• central nervous system
• autonomic nervous system

Question 5

In nicotinic receptors, what subunit exists rather than the epsilon subunit in fetuses?

Answer 5

gamma

Question 6

What makes up the pentamer in skeletal muscle nicotinic receptors?

Answer 6

2 alpha 1 subunits, an epsilon subunit, and delta, and a beta 1 subunit

Question 7

Neuronal nicotinic receptor (alpha 4, beta 7, alpha 7 subtypes) are located where? and what is their role

Answer 7

Pre-synaptic nerve terminals and on neuronal axons
Role: neuronal modulation - modulate the release of ACh and other neurotransmitters

Question 8

Autonomic nicotinic receptors (alpha 3 and beta 4) - their roles are what?

Answer 8

Similar to that in skeletal muscle - trigger an action potential in post-ganglionic neuron and ensure the signal is sent down to autonomic effector tissues

Question 9

Which transmembrane domain in the nicotinic acetylcholine receptor subunits forms the lining of the ion channel?

Answer 9

2

Question 10

How many binding sites for acetylcholine are there in the muscle nicotinic receptor?

Answer 10

2

Question 11

How is signalling via acetylcholine terminated at the neuromuscular junction?

Answer 11

enzymatic degradation of the signal (ACh is broken down by acetylcholinesterase - this is the same process at all cholinergic terminals)

Question 12

Where is the agonist binding site in nicotinic receptors?

Answer 12

In the terminal domains (the N terminus)

Question 13

Where is the agonist binding site in family A receptors?

Answer 13

Buried down in the transmembrane domains

Question 14

Agonists in M1 receptors could potentially be used to treat what? (2)

Answer 14

Alzheimer’s Disease + Schizophrenia

Question 15

Antagonists at the M1 receptor could potentially be used to treat what?

Answer 15

Potential therapies for certain cancers

Question 16

What is darifenacin useful for?

Answer 16

30 fold M3 selective (overactive bladder)

Question 17

Where are colinergic neurons present?

Answer 17

Cholinergic neurons are present in the CNS and also play major roles in the autonomic nervous system (particularly the parasympathetic branch)

Question 18

Muscarinic M2 and M4 receptors can act as what?

Answer 18

As presynaptic autoreceptors.

Question 19

What do muscarinic M2 and M4 receptors do, and what kind of feedback loop is this?

Answer 19

They inhibit the release of ACh from the presynaptic nerve terminal. This is a form of negative feedback

Question 20

The post synaptic cell can be what?

Answer 20

Any tissue innervated by the parasympathetic nervous system e.g. smooth muscle, cardiac muscle, gland. Muscarinic receptors are also found in the CNS, so this could also be another CNS neuron.

Question 21

Describe the function/applications of muscarinic agonists

Answer 21

They are not widely used, but many potential applications for antagonists as mAChR are widespread in the parasympathetic NS and the CNS.

Question 22

Describe the function/applications of muscarinic antagonists

Answer 22

Peripheral effects mostly by blocking the parasympathetic nervous system = parasympatholytic drugs

Question 23

Describe atropine (3)

Answer 23

• non-selective
• treats bradycardia (M2 receptors SA node)
• nerve agent antidote

Question 24

Describe hyoscine (scopolamine) (3)

Answer 24

• non-selective
• nausea, motion sickness, IBS
• mods reduce blood brain barrier penetration

Question 25

Describe ipratropium/tiotropium

Answer 25

• target

Question 26

Describe ipratropium/tiotropium (2)

Answer 26

• target M3 receptors in bronchial smooth muscle
• used in COPD and asthma

Question 27

Describe glycopyrrolate (glycopyrronium) (4)

Answer 27

• non-selective
• used as surgery premedication
• given with AChE inhibitors
• can treat excessive sweating

Question 28

Describe benzatropine (benztropine) (2)

Answer 28

• M1 selective antagonist
• treats movement disorders (parkinson’s)

Question 29

Describe darifenacin (2)

Answer 29

• M3 selective (30-fold vs M2)
• used to treat overactive bladder syndrome

Question 30

Describe cyclopentolate/tropicamide (3)

Answer 30

• used to produce mydriasis (pupil dilation) and cycloplegia (paralysis of accommodation)
• shorter duration than atropine
• causes light sensitivity

Question 31

Which muscarinic receptor subtypes couple to the IP3 pathway via Gq?

Answer 31

M1, M3, M5

Question 32

Which muscarinic receptor type is heavily expressed in the heart?

Answer 32

M2

Question 33

Where is the allosteric site on muscarinic receptors?

Answer 33

Just above the agonist binding site

Question 34

What are the alpha agonist potency rankings?

Answer 34

noradrenaline > adrenaline > isoprenaline

Question 35

What are the beta agonist potency rankings?

Answer 35

isoprenaline > adrenaline > noradrenaline

Question 36

What enzyme is involved in the breakdown of noradrenaline?

Answer 36

Monoamine oxidase - located on the mitochondrial membrane - regulates the pool of releasable noradrenaline

Question 37

What protein is key to terminating signaling at adrenergic synapses?

Answer 37

NET (norepinephrine transporter)

Question 38

Precursors of noradrenaline include: (3)

Answer 38

• dopamine
• tyrosine
• L-DOPA

Question 39

Adenylate cyclase and phospholipase C are the enzymes that initiate signalling via cAMP and IP3 respectively. Which subtypes of adrenoceptor have stimulatory effects on these enzymes? (3)

Answer 39

Alpha 1, Beta 1, Beta 2 : alpha 1 is coupled to Gq and stimulates PLC and the beta receptors both stimulate adenylate cyclase via Gs

Question 40

From what region do the parasympathetic neurones that target the lower GI tract leave the spinal cord?

Answer 40

sacral

Question 41

When a parasympathetic neuron makes a synapse with its target tissue, which neurotransmitter does it usually release?

Answer 41

Acetylcholine