M1i: Outline the production, release & fate of noradrenaline at the sympathetic nerve terminal
- Catecholamine = an organic compound consisting of a catechol & an amino side chain
- Catechol = benzene ring with 2 hydroxyl side groups at C3 and C4
Synthesis
- Occurs in cytoplasm of adrenergic neurons & chromaffin cells of adrenal medulla
- Formed from TYROSINE
- Tyrosine can be dietary or from phenylalanine
- TYROSINE → DOPA (Tyrosine hydroxylase) → rate limiting step
- DOPA → DOPAMINE (DOPA decarboxylase)
- Dopamine enters storage vesicles
- DOPAMINE → NA (Dopamine-β-hydroxylase)
- In the adrenal medulla only:
- NA → Adrenaline (PNMT)
- Catecholamines remain in vesicles until their release
Release
- Repolarisation of nerve allows Ca2+ influx
- Exocytosis of vesicles → releases NA into junctional space
- Adrenal medulla → releases NA & Adrenaline
- Post-ganglionic symp. neurons → Release NA
- Sympathetic ganglia → interneurons use Dopamine as their NT
Inactivation
- NA released from nerve terminal lasts ~10secs
- It is removed by 3 mechanisms:
1) Reuptake
- Back into nerve terminal
- Here it can be:
- Stored in vesicles → for re-release
- Metabolised by MAO
2) Diffusion
- Away from synaptic cleft
- Eventually metabolised in plasma, lungs, liver
3) Metabolism
- By tissue enzymes COMT & MAO
- MAO formed on outer surface of mitochondria ∴ ‘intracellular enzyme’
- MAO found in neurons which release NA, liver, kidney, intestinal mucosa
- MAO deaminates removing the NH2
- COMT is extraneuronal
- Present in cytoplasm of liver, kidney, smooth m.
- It methylates a hydroxyl group to produce normetanephrine
- If normetanephrine is not metabolised it is deaminated by MAO to form VMA
- NB: MAO inhibitors ↑[NA]+++, COMT inhibitors do not

