DGN - Neurotransmission in the ANS Flashcards
What historical experiment provided evidence that the sympathetic nervous system releases an adrenaline-like compound?
The Finkelman preparation
Who demonstrated that nor-adrenaline is the main endogenous catecholamine in the sympathetic nerves?
Von Euler
What are the 4 main steps in the sympathetic synapse?
1) Synthesis
2) Release
3) Inactivation
4) Receptors
What 4 steps are involved in the synthesis of adrenaline from tyrosine?
1) An -OH group is added to the ring on tyrosine structure via tyrosine hydroxylase
- (Forms L-DOPA)
2) The -COOH group is removed from L-DOPA via dopadecarboxylase
- (Forms Dopamine)
3) An -OH group is added to the beta carbon on Dopamine via dopaminebetahydroxylase
- (Forms Noradrenaline)
4) A methyl (-CH3) group is added to the amino group on Noradrenaline via PNMT
- (Forms Adrenaline)
Name a drug that is a competitive inhibitor of tyrosine hydroxylase?
α methyl-tyrosine
- used in the treatment of phaeochromocytoma
How does α methyl-DOPA interfere with NAdr transmission?
It leads to the synthesis of the false transmitter α methyl-NAdr
What enzyme does Carbidopa inhibit?
Dopa decarboxylase (DCC)
- Used in the treatment of Parkinson’s disease
Where is NADR stored?
In vesicles with ATP and Chromogranin
Name drugs that interfere with NAdr storage (3)
- Rauwolfia
- Reserpine
- Guanethidine
What was demonstrated by IVERSEN regarding the inactivation of NAdr following release?
Used radio labelled Noradrenaline
Used tissue receiving sympathetic innervation, cardiac tissue
Measured amount of noradrenaline accumulated by intact and denervated tissue
The presence of UPTAKE mechanisms for NAdr
What are some features of the UPTAKE 1 mechanism? (5)
NAT (Noradrenaline transporter)
- High affinity
- Low capacity
- NERVE TERMINAL
- Requires Na+ gradient and ATP
- Substrate specific for NAdr
What are some fratures of the UPTAKE 2 mechanism? (4)
- Low affinity
- High Capacity
- EXTRANEURONAL
- Inhibited by cortisol
- Not substrate specific (removes other NT)
Which drugs block UPTAKE 1, increasing the action of NAdr? (6)
- Antidepressants
- Cocaine
- Imipramine (First Tricyclic antidepressant)
- Desipramine
- Amitryptaline
- Guanethidine
Name 4 drugs that stimulate NAdr release
1) Indirect sympathominetics
2) TYRAMINE
- naturally occurring in foodstuffs
3) EPHEDRINE
- used in cold remedies
4) AMPHETAMINE
- psychostimulant
What are the two enzymes involved in NAdr metabolism?
- Monoamine Oxidase (MAO)
- Catechol-O-Methyl Transferase (COMT)
