Lecture 9. Purinergic Signalling

Question 1

What are examples of adenine nucleotide signalling molecules?

Answer 1

ATP
ADP

Question 2

What are examples of adenine nucleoside signalling molecules?

Answer 2

Adenosine

Question 3

What is the neurotransporter for ATP?

Answer 3

VNUT (vesicular nucleotide transporter)

Question 4

How is ATP contained within vesicles released?

Answer 4

Through exocytosis

Question 5

What is the role of ATP as a neurotransmitter?

Answer 5

To act as a cotransmitter for other molecules

Question 6

How else can ATP be release (outside of vesicles)

Answer 6

Through leakage caused by tissue damage

Question 7

What receptors does ATP activate?

Answer 7

P2X receptors (ligand-gated ion channels)
P2Y (G-protein-coupled receptors)

Question 8

What enzymes metabolise ATP into ADP, AMP and adenosine?

Answer 8

Nucleotidases

Question 9

What receptor does ADP activate?

Answer 9

P2Y (G-protein-coupled receptors)

Question 10

What receptor does adenosine activate?

Answer 10

P1

Question 11

What is the adenosine transporter?

Answer 11

Equilibrative transporter that either removes or uptakes adenosine into the cell depending on the extracellular concentration

Question 12

How many subtypes of P2X are there?

Answer 12

7

Question 13

How many subtypes of P2Y are there?

Answer 13

8 (1-4, 6, 11-14)

Question 14

What P2Y subtypes are activated by ATP?

Answer 14

2 & 11

Question 15

What P2Y subtypes are activated by ADP?

Answer 15

1, 12, 13

Question 16

How many subtypes of P1 are there?

Answer 16

4 (1, 2A, 2B, 3)

Question 17

What activates the P0 receptor?

Answer 17

Adenine

Question 18

What does α,β,methylene-ATP do?

Answer 18

Desensitises P2X receptors

Question 19

Depending on the tissue, what can ATP signalling cause?

Answer 19

Contraction or inhibition

Question 20

What are suramin and PPADS?

Answer 20

P2X receptor antagonists

Question 20

What type of ligand-gated ion channels do ATP P2X receptors form?

Answer 20

Trimeric ligand-gated ion channels

Question 21

What type of ligand-gated ion channels do glutamate receptors form?

Answer 21

Tetrameric

Question 22

What type of ligand-gated ion channels do nicotinic receptors form?

Answer 22

Pentameric

Question 23

Why is the TM2 domain important?

Answer 23

Forms the pore of the ion channel

Question 24

Where might you see purinergic signalling?

Answer 24

Pain pathways

Question 25

How can analgesia be achieved in pain pathways?

Answer 25

Utilising P2X antagonists or A₁ agonists

Question 26

What cells release ATP that signals for pain?

Answer 26

Tumour cells Endothelial cells Merkel cells

Question 27

What does adenosine provide through A₁ receptors?

Answer 27

Initialising pain killing mechanisms

Question 28

How does ATP stimulate the coughing reflex?

Answer 28

Release of ATP activates P2X₃ receptors on nerve fibres that trigger a cough

Question 29

When are P2X₇ receptors activated?

Answer 29

In very high concentrations of ATP

Question 30

How can pathological activation of P2X₇ receptors cause damage?

Answer 30

Excessive influx of Na⁺ and Ca²⁺ into the cell causes cell damage

Question 31

How is P2X₇ linked to Chron's disease?

Answer 31

Less abdominal pain in patients who took P2x₇ antagonists

Question 32

What are P2Y receptors involved in?

Answer 32

Controlling platelet aggregation (can also lead to thrombosis in atherosclerosis)

Question 33

What are the P2Y₁-like subfamily?

Answer 33

P2Y₁-P2Y₁₁

Question 34

What are the P2Y₁₂-like subfamily?

Answer 34

P2Y₁₂-P2Y₁₄

Question 35

What is an example of a P2Y₁₂ antagonist?

Answer 35

Clopidogrel

Question 36

What are alladenosine (P1) receptors?

Answer 36

G protein coupled receptors

Question 37

What G protein are A1 receptors coupled with?

Answer 37

Gαi

Question 38

What G protein are A2A receptors coupled with?

Answer 38

Gαs

Question 39

What G protein are A2B receptors coupled with?

Answer 39

Gαs & Gαq

Question 40

What G protein are A3 receptors coupled with?

Answer 40

Gαi

Question 41

What is the function of the A1 receptor?

Answer 41

Bradycardia; antinociception; reduction of sympathetic and parasympathetic activity; neuronal hyperpolarisation; ischemic preconditioning

Question 42

What is the function of the A2A receptor?

Answer 42

Inhibition of platelet aggregation; vasodilatation, protection against ischemic damage; wound healing

Question 43

What is the function of the A2B receptor?

Answer 43

Relaxation of smooth muscle in vasculature and intestine

Question 44

What is the function of the A3 receptor?

Answer 44

Enhancement of mediator release from mast cells (some A3 species); preconditioning (some species)

Question 45

What is the effect of adenine-based purines as nervous system modulators?

Answer 45

Decrease in heart rate and blood pressure

Question 46

What does adenosine act as in the heart?

Answer 46

A cardiac "retaliatory metabolite"

Question 47

What heart condition is adenosine used to treat?

Answer 47

Superventricular tachycardia

Question 48

What structure releases lots of adenosine following a seizure (particularly in the epileptic)?

Answer 48

Hippocampus

Question 49

What enzyme can influence the activity of seizures?

Answer 49

Adenosine kinase