Lesson 12

Purinergic Neurotransmitters

• ATP, ADP, and adenosine are purinergic neurotransmitters.
• Purinergic receptors:
  • Ionotropic: P2X family
  • Metabotropic: P1, P2Y families.
• Neuropeptides are usually co-released with other transmitters and act on metabotropic receptors, affecting postsynaptic cell excitability.

Nitric Oxide (NO)

• NO is a universal intercellular messenger, can act autocrine and paracrine.
• NO is lipid-soluble, diffuses easily across membranes.
• Synthesized from L-arginine via nitric oxide synthase (NOS).
• Key role in central sensitization to pain.
• Effects mediated by soluble guanylyl cyclase producing cGMP from GTP.

Purinergic Neurotransmission

• Purines and pyrimidines are foundational in cellular functions and include:
  • DNA/RNA precursors
  • Energy carriers (ATP, ADP)
  • Allosteric enzyme modulators
• Adenosine is generated from ATP by ectonucleotidase; plays roles in sleep regulation and tissue protection.
• Purinergic neurotransmitters metabolized to 5'-AMP to terminate effects.

Neuropeptide Neurotransmission

• Neuropeptides classified by anatomical location or chemical similarities. Examples include:
  • Hypothalamic peptides
  • Opioid peptides
  • Neuropeptide Y, Substance P, VIP/glucagon family.

NO Synthesis and Action

• NO synthesized from L-arginine; depends on NOS types:
  1. NOS1 (nNOS)
  2. NOS2 (iNOS)
  3. NOS3 (eNOS)
• Low concentrations of NO as signaling molecule; high concentrations can be cytotoxic.

Effects of NO in the CNS and PNS

• NO influences sleep, feeding behavior, gastrointestinal function.
• It's crucial in synaptic plasticity (LTP and LTD) and memory formation.
• Important for vascular tone control; synthesized by endothelial cells.