Noradrenaline / Adrenaline

Noradrenaline / Adrenaline

1. Produced by sympathetic nerves and adrenal medulla

   • Adrenal cortex produced adrenaline
     • Adrenaline = similar to stimulating sympathetic nerves

2. Parasympathetic

   • Nerves coming from brain and sacral parts of spinal cord

3. Sympathetic

   • Nerves coming from thoracic and lumber parts of spinal cord
   • Fight/flight
   • Gut
     • Decreased motility
     • Increased sphincter tone
   • Heart
     • Increased rate and force of attraction
   • Iris
     • Pupil dilation
   • Liver
     • Glycogen --> glucose
   • Adrenal medulla
     • Increase adrenaline production
   • Two neurones
     • Pre
     • Post
       • Releases Noradrenaline
         • and ATP
       • Branch in the periphery

4. Enteric

5. Synthesis of catecholamines

   • Tyrosine
     • E - Tyrosine hydroxylase
       • Dihydroxyphenylalanine
         • E - DOPA decarboxylase
           • Dopamine
             • E- dopamine beta hydroxylase
               • Noradrenaline
                 • E - Phenylethanolamine N-methyl transferase
                   • Adrenaline
                   • Only present in adrenal medulla
                     • Why neurones only produce Nad
                   • PNMT
                 • Increasing amount inhibits Tyrosine Hydroxylase
             • Centrally acting NTM
           • Inhibited by carbidopa
             • Used clinically for parkinsons
               • To prevent dopamine for being formed in the periphery
             • stays in the brain
         • DOPA
           • Treatment for parkinsons
       • Rate limiting step
       • Inhibited by alpha methyltyrosine

6. Storage

   • NAd and Ad = stored in membrane limited particles
     • Chromaffin granules
     • Small vesicles = 50nm
       • Varicosities
     • Large vesicles = 80nm
       • Cell body, axon and varicosities
     • VMAT takes dopamine into vesicles
       • Requires H+
         • H+ out Catech in
           • Therefore vesicles have H+ pump
             • ATPase
       • Dopamine --> noradrenaline inside vesicle
       • Inhibitor of VMAT
         • Reseprine
           • Neurotransmitter release decreases
           • Good
             • Reduces hypertension
               • Decreased sympathetic nerve stimulation to heart
           • Bad
             • Effects CNS
               • Leads to depression
     • VNUT
       • Allows ATP entry

7. Exocytosis

   • Action potential
     • Depolorisation
       • Ca2+ entry
         • Activation of ca2+ sensitive proteins
           • Vesicles fuse with nerve terminal
             • Release of contents
   • Could effect any of the mechanisms to the left
     • Would effect all nerve terminals
   • Release of NAd and chromagrannin but no lipid release
     • Supports vesicle rellease
   • Botulinum effects exocytosis
   • Prejunctional regulation of Ex
     • Alpha 2 receptors on nerve terminal
       • Feedback mechanism
     • ACh receptors
     • Opiate receptors
       • Present on autonomic nerve terminals
         • Inhibit NA release

8. Termination

   • Uptake
     • Into the presynaptic nerve terminal
       • Uptake 1
       • NAT
         • Selective from Nad
         • Can be inhibited
           • Antidepressents
           • Cocaine
             • Also local anaesthetic
           • Noradrenaline hangs around for longer
             • Activates receptors
               • Amplification of sympathetic activity
         • Closely related to dopamine and serotonin transporter
           • How they effect depression
     • Into other cells
       • Uptake 2
         • Muscle cellls
         • Endothelium
   • Degradation
     • Monamine oxidases and COMT degrade catech
       • Targeted with drugs
         • Inhibitors enhance effects of noradrenaline
       • MAO
         • Drugs treat depression
           • Amplify cat in the brain
       • COMT
         • Treat parkinsons
       • Metabolite = VMA
         • Can measure this in the urine

9. Noradrenergic neuron blocking drugs

   • Inhibit noradrenaline release from Sym NT
     • Inhibit ONLY symp
       • As are substrates for NAT
         • Transported into the nerve terminal

10. Indirectly acting sympathetic amines

    • Uptaken by VMAT
      • Displace NAd
        • Release of Nad
          • Similar effect on dopamine and 5-HT in CNS
          • Activates the receptors
      • Enter vesicles
    • Enter nerve terminals

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