Pharmacology of Peripheral Neural Transmission (NANCs)

Question 1

Which NANCs are associated with ACh neurones?

Answer 1

1. ATP
2. VIP

Question 2

Which NANCs are associated with NA neurones?

Answer 2

1. ATP
2. NPY

Question 3

What are the mechanisms by which NANCs can act?

Answer 3

1. Mediates neurotransmission by binding to post-synaptic ion channels.
2. Acts as neuromodulators by binding to post-synaptic receptors (mainly GPCRs) to change effect of NT.
3. Act on further targets due to being broken down much more slowly.

Question 4

What are the affinities of P1 receptors for purinergic transmitters?

Answer 4

Adenosine > AMP > ADP > ATP

Question 5

What are the affinities of P2 receptors for purinergic transmitters?

Answer 5

ATP > ADP > AMP > Adenosine

Question 6

What are the different classes of purinergic receptors?

Answer 6

1. Adenosine (P1) receptors - GPCRs
2. P2X receptors - LGICs
3. P2Y receptors - GPCRs

Question 7

How is ATP packaged into vesicles?

Answer 7

Vesicular nucleotide transporter (VNUT)

Question 8

How is ATP released during transmission?

Answer 8

1. Exocytosis from vesicles
2. Nucleoside transporters (e.g. pannexins)

Question 9

What is the structure of P2X receptors?

Answer 9

• Each isoform contains 2 transmembrane domains
• Isoforms assemble into homo-/heterotrimers to form functional recepotors

Question 10

What is the role of P2X receptors in PNS?

Answer 10

• ATP co-released with NA/ACh
• Causes fast component of smooth muscle contraction (P2X) followed by slower contraction caused by NT (α-adrenoreceptor)

Question 11

What is the role of P2X receptors in sensation?

Answer 11

1. Important in transduction mechanisms of some special senses (e.g. taste)
2. Important in mediating sensation of distension in bladder

Question 12

How is adenosine produced?

Answer 12

1. Breakdown product of ATP by ectodonucleases
2. Produced intracellularly by endonucleases and is released if rate of production exceeds rate of metabolism

Question 13

What is the role of adenosine in cardiac tissue?

Answer 13

1. Produced in cardiac tissue during hypoxia
2. Rate of production exceeds rate of metabolism
3. Released into ECF
4. Binds to A₁ receptors and causes reduced heart rate/contractility
5. Reduces work of heart and protects against damage

Question 14

What is the role of NO in the PNS?

Answer 14

Nitrergic (NO-releasing) neurones mediate muscle tone of several sphincters of the GI tract (e.g. lower oesophagus, pylorus…), upper airways and male reporductive organ

Question 15

How is neuropeptide release stimulated?

Answer 15

Repetitive APs → ↑ general [Ca²⁺] (as opposed to local for NTs)

Question 16

What are the effects of neuropeptide release in autonomic ganglia?

Answer 16

Responsible for late slow EPSP