Adrenergic Transmission (noradrenaline transmission) Flashcards
Where is the best site for drug intervention in sympathetic transmission and why?
At the neuroeffector junction - allows for specific targeting of function.
If CNS or sympathetic ganglia were targeted, the effects would be non-specific and likely widespread.
How is noradrenaline synthesised?
From tyrosine.
Tyrosine > DOPA > Dopamine > Noradrenaline >Adrenaline
What enzyme converts tyrosine to DOPA?
Tyrosine hydroxylase
How can conversion of tyrosine to DOPA be inhibited?
By α-methyl-tyrosine inhibiting tyrosine hydroxylase (competitive inhibition)
What enzyme converts DOPA to dopamine?
DOPA decarboxylase
What enzyme converts dopamine to noradrenaline?
Dopamine β-hydroxylase
What enzyme converts noradrenaline to adrenaline?
Phenylethanol-amine N-methyl transferase
What is the effect of α-methyl-tyrosine?
Reduced DOPA production > reduced noradrenaline
Less sympathetic effect > decreases blood pressure.
Side effects: sedation, Parkinsonism, Diarrhoea.
How is noradrenaline stored?
In vesicles (transported in via VMAT) If not in vesicles will be broken down by monoamineoxidase (MAO)
What drug inhibits noradrenaline storage? What is the effects of the drug?
Reserpine.
Blocks VMAT - prevents storage in vesicles.
Noradrenaline will be broken down by monoamineoxidase. - Depletes neurons of NA
Used as an antihypertensive.
What drug inhibits noradrenaline release? How does it work?
Clonidine.
Normally α2 receptors have a negative feedback mechanism to reduce NA release once activate.
Clonidine in an V2 agonist - stimulates receptor as NA would - prevents further NA release.
What drugs promote noradrenaline release and how do they work?
Amphetamines.
Enter the pre-ganglionic neuron via uptake-1 channels and displace NA in vesicles.
Amphetamines also inhibits monoamineoxidase hence less NA is broken down so more is free for release across synapse.
What are the 3 types of G-protein and which adrenergic receptors are they associated to?
Gq -α1 receptor
Gi - α2 receptor
Gs - β1,2,3 receptors
What is the signalling pathway of an α1 receptor?
Gq protein coupled.
Activates phospholipase C.
PIP3 > IP3 + DAG
IPs increases Ca2+ concentration from sarcoplasmic reticulum.
DAG activate protein kinase C.
Ultimately leads to smooth muscle contraction.
What is the signalling pathway of an α2 receptor?
Gi coupled. Inhibits adenylylcylase. Decreased cAMP production. Decreased protein kinase A activation Decreased exocytosis - inhibits neurotransmitter release.