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LF261: Neuropharmacology > Lecture 9. Purinergic Signalling > Flashcards

Lecture 9. Purinergic Signalling Flashcards

1
Q

What are examples of adenine nucleotide signalling molecules?

A

ATP
ADP

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2
Q

What are examples of adenine nucleoside signalling molecules?

A

Adenosine

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3
Q

What is the neurotransporter for ATP?

A

VNUT (vesicular nucleotide transporter)

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4
Q

How is ATP contained within vesicles released?

A

Through exocytosis

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5
Q

What is the role of ATP as a neurotransmitter?

A

To act as a cotransmitter for other molecules

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6
Q

How else can ATP be release (outside of vesicles)

A

Through leakage caused by tissue damage

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7
Q

What receptors does ATP activate?

A

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

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8
Q

What enzymes metabolise ATP into ADP, AMP and adenosine?

A

Nucleotidases

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9
Q

What receptor does ADP activate?

A

P2Y (G-protein-coupled receptors)

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10
Q

What receptor does adenosine activate?

A

P1

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11
Q

What is the adenosine transporter?

A

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

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12
Q

How many subtypes of P2X are there?

A

7

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13
Q

How many subtypes of P2Y are there?

A

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

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14
Q

What P2Y subtypes are activated by ATP?

A

2 & 11

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15
Q

What P2Y subtypes are activated by ADP?

A

1, 12, 13

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16
Q

How many subtypes of P1 are there?

A

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

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17
Q

What activates the P0 receptor?

A

Adenine

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18
Q

What does α,β,methylene-ATP do?

A

Desensitises P2X receptors

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19
Q

Depending on the tissue, what can ATP signalling cause?

A

Contraction or inhibition

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20
Q

What are suramin and PPADS?

A

P2X receptor antagonists

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20
Q

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

A

Trimeric ligand-gated ion channels

21
Q

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

A

Tetrameric

22
Q

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

A

Pentameric

23
Q

Why is the TM2 domain important?

A

Forms the pore of the ion channel

24
Q

Where might you see purinergic signalling?

A

Pain pathways

25
Q

How can analgesia be achieved in pain pathways?

A

Utilising P2X antagonists or A₁ agonists

26
Q

What cells release ATP that signals for pain?

A

Tumour cells
Endothelial cells
Merkel cells

27
Q

What does adenosine provide through A₁ receptors?

A

Initialising pain killing mechanisms

28
Q

How does ATP stimulate the coughing reflex?

A

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

29
Q

When are P2X₇ receptors activated?

A

In very high concentrations of ATP

30
Q

How can pathological activation of P2X₇ receptors cause damage?

A

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

31
Q

How is P2X₇ linked to Chron’s disease?

A

Less abdominal pain in patients who took P2x₇ antagonists

32
Q

What are P2Y receptors involved in?

A

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

33
Q

What are the P2Y₁-like subfamily?

A

P2Y₁-P2Y₁₁

34
Q

What are the P2Y₁₂-like subfamily?

A

P2Y₁₂-P2Y₁₄

35
Q

What is an example of a P2Y₁₂ antagonist?

A

Clopidogrel

36
Q

What are all adenosine receptors?

A

G protein coupled receptors

37
Q

What G protein are A1 receptors coupled with?

A

Gαi

38
Q

What G protein are A2A receptors coupled with?

A

Gαs

39
Q

What G protein are A2B receptors coupled with?

A

Gαs & Gαq

40
Q

What G protein are A3 receptors coupled with?

A

Gαi

41
Q

What is the function of the A1 receptor?

A

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

42
Q

What is the function of the A2A receptor?

A

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

43
Q

What is the function of the A2B receptor?

A

Relaxation of smooth muscle in vasculature and intestine

44
Q

What is the function of the A3 receptor?

A

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

45
Q

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

A

Decrease in heart rate and blood pressure

46
Q

What does adenosine act as in the heart?

A

A cardiac “retaliatory metabolite”

47
Q

What heart condition is adenosine used to treat?

A

Superventricular tachycardia

48
Q

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

A

Hippocampus

49
Q

What enzyme can influence the activity of seizures?

A

Adenosine kinase

LF261: Neuropharmacology (15 decks)

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