Autonomic Physiology — Noradrenaline Synapse

Sympathetic Nervous System

• Short pre-ganglionic B fibres terminating at the paravertebral sympathetic chain → Synapse with postganglionic fibres and release Ach
• Long post-ganglionic fibres innervating target tissues → Release noradrenaline (Except sweat glands and adrenals)

Noradrenaline

• Naturally occuring catecholamine derived from catecholamine
• Direct α adrenoceptor agonist with partial β adrenoceptor agonism
  • Peripheral vasoconstriction with increased MAP and diastolic pressures

Production

• Derived from tyrosine
  • Tyrosine → L-DOPA (Tyrosine hydroxylase)
  • L-DOPA → Dopamine (Dopa decarboxylase)
  • Dopamine → Nordrenaline (Dopamine hydroxylase)
  • Noradrenaline → Adrenaline (PMNT)

• Enzymes required for noradrenaline synthesis present widely in peripheral sympathetic neurons
• Tyrosine hydroxylase is the rate limiting step and can be upregulated by PKA phosphorylation
• Noradrenaline stored in vesicles in post-ganglionic sympathetic nerve terminals – Vesicular Monoamine Transporter (VMAT2)

Release

• On action potential arrival at sympathetic nerve terminal
• Specific mechanisms for catecholamine release are unknown, however thought to be due to increased [Ca²⁺] at the nerve terminal in response to action potential
• Vesicles fuse with cell membrane and contents released into the nerve-effector junction

Fate

• Noradrenaline released from nerve terminal binds to adrenergic G Protein Coupled Receptors on target tissues causing various sympathetic effects
• Noradrenaline binds to prejunctional α₂ receptors preventing further noradrenaline release
• NET proteins cause re-uptake of noradrenaline into nerve terminals where they may be metabolized by monoamine oxidase (MAO) enzymes or repackaged into neurotransmitter vesicles
• Noradrenaline can diffuse away from the junctional cleft into the systemic circulation and metabolized by Catechol O-Methyl Transferase (COMT) enzymes in liver and other tissues
• Metabolites → VMA and Normetadrenaline → renal elimination

Sakurai 2016

Answer by Sakurai