Lecture 9. Purinergic Signalling Flashcards
What are examples of adenine nucleotide signalling molecules?
ATP
ADP
What are examples of adenine nucleoside signalling molecules?
Adenosine
What is the neurotransporter for ATP?
VNUT (vesicular nucleotide transporter)
How is ATP contained within vesicles released?
Through exocytosis
What is the role of ATP as a neurotransmitter?
To act as a cotransmitter for other molecules
How else can ATP be release (outside of vesicles)
Through leakage caused by tissue damage
What receptors does ATP activate?
P2X receptors (ligand-gated ion channels)
P2Y (G-protein-coupled receptors)
What enzymes metabolise ATP into ADP, AMP and adenosine?
Nucleotidases
What receptor does ADP activate?
P2Y (G-protein-coupled receptors)
What receptor does adenosine activate?
P1
What is the adenosine transporter?
Equilibrative transporter that either removes or uptakes adenosine into the cell depending on the extracellular concentration
How many subtypes of P2X are there?
7
How many subtypes of P2Y are there?
8 (1-4, 6, 11-14)
What P2Y subtypes are activated by ATP?
2 & 11
What P2Y subtypes are activated by ADP?
1, 12, 13
How many subtypes of P1 are there?
4 (1, 2A, 2B, 3)
What activates the P0 receptor?
Adenine
What does α,β,methylene-ATP do?
Desensitises P2X receptors
Depending on the tissue, what can ATP signalling cause?
Contraction or inhibition
What are suramin and PPADS?
P2X receptor antagonists
What type of ligand-gated ion channels do ATP P2X receptors form?
Trimeric ligand-gated ion channels
What type of ligand-gated ion channels do glutamate receptors form?
Tetrameric
What type of ligand-gated ion channels do nicotinic receptors form?
Pentameric
Why is the TM2 domain important?
Forms the pore of the ion channel
Where might you see purinergic signalling?
Pain pathways
How can analgesia be achieved in pain pathways?
Utilising P2X antagonists or A₁ agonists
What cells release ATP that signals for pain?
Tumour cells
Endothelial cells
Merkel cells
What does adenosine provide through A₁ receptors?
Initialising pain killing mechanisms
How does ATP stimulate the coughing reflex?
Release of ATP activates P2X₃ receptors on nerve fibres that trigger a cough
When are P2X₇ receptors activated?
In very high concentrations of ATP
How can pathological activation of P2X₇ receptors cause damage?
Excessive influx of Na⁺ and Ca²⁺ into the cell causes cell damage
How is P2X₇ linked to Chron’s disease?
Less abdominal pain in patients who took P2x₇ antagonists
What are P2Y receptors involved in?
Controlling platelet aggregation (can also lead to thrombosis in atherosclerosis)
What are the P2Y₁-like subfamily?
P2Y₁-P2Y₁₁
What are the P2Y₁₂-like subfamily?
P2Y₁₂-P2Y₁₄
What is an example of a P2Y₁₂ antagonist?
Clopidogrel
What are alladenosine (P1) receptors?
G protein coupled receptors
What G protein are A1 receptors coupled with?
Gαi
What G protein are A2A receptors coupled with?
Gαs
What G protein are A2B receptors coupled with?
Gαs & Gαq
What G protein are A3 receptors coupled with?
Gαi
What is the function of the A1 receptor?
Bradycardia; antinociception; reduction of sympathetic and parasympathetic activity; neuronal hyperpolarisation; ischemic preconditioning
What is the function of the A2A receptor?
Inhibition of platelet aggregation; vasodilatation, protection against ischemic damage; wound healing
What is the function of the A2B receptor?
Relaxation of smooth muscle in vasculature and intestine
What is the function of the A3 receptor?
Enhancement of mediator release from mast cells (some A3 species); preconditioning (some species)
What is the effect of adenine-based purines as nervous system modulators?
Decrease in heart rate and blood pressure
What does adenosine act as in the heart?
A cardiac “retaliatory metabolite”
What heart condition is adenosine used to treat?
Superventricular tachycardia
What structure releases lots of adenosine following a seizure (particularly in the epileptic)?
Hippocampus
What enzyme can influence the activity of seizures?
Adenosine kinase
