Pharmacology of Peripheral Neural Transmission (NANCs) Flashcards
Which NANCs are associated with ACh neurones?
- ATP
- VIP
Which NANCs are associated with NA neurones?
- ATP
- NPY
What are the mechanisms by which NANCs can act?
- Mediates neurotransmission by binding to post-synaptic ion channels.
- Acts as neuromodulators by binding to post-synaptic receptors (mainly GPCRs) to change effect of NT.
- Act on further targets due to being broken down much more slowly.
What are the affinities of P1 receptors for purinergic transmitters?
Adenosine > AMP > ADP > ATP
What are the affinities of P2 receptors for purinergic transmitters?
ATP > ADP > AMP > Adenosine
What are the different classes of purinergic receptors?
- Adenosine (P1) receptors - GPCRs
- P2X receptors - LGICs
- P2Y receptors - GPCRs
How is ATP packaged into vesicles?
Vesicular nucleotide transporter (VNUT)
How is ATP released during transmission?
- Exocytosis from vesicles
- Nucleoside transporters (e.g. pannexins)
What is the structure of P2X receptors?
- Each isoform contains 2 transmembrane domains
- Isoforms assemble into homo-/heterotrimers to form functional recepotors
What is the role of P2X receptors in PNS?
- ATP co-released with NA/ACh
- Causes fast component of smooth muscle contraction (P2X) followed by slower contraction caused by NT (α-adrenoreceptor)
What is the role of P2X receptors in sensation?
- Important in transduction mechanisms of some special senses (e.g. taste)
- Important in mediating sensation of distension in bladder
How is adenosine produced?
- Breakdown product of ATP by ectodonucleases
- Produced intracellularly by endonucleases and is released if rate of production exceeds rate of metabolism
What is the role of adenosine in cardiac tissue?
- Produced in cardiac tissue during hypoxia
- Rate of production exceeds rate of metabolism
- Released into ECF
- Binds to A1 receptors and causes reduced heart rate/contractility
- Reduces work of heart and protects against damage
What is the role of NO in the PNS?
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
How is neuropeptide release stimulated?
Repetitive APs → ↑ general [Ca2+] (as opposed to local for NTs)