Adrenergic Pharmacology 2

Question 1

What is the definition of rate limiting step and what is the rate limiting step in catecholamine synthesis?

Answer 1

• Slowest step of the whole pathway that determines the rate at which the whole pathway proceeds
• Tyrosine hydroxylase

Question 2

What are the major catecholamines?

Answer 2

• Dopamine
• Noradrenaline
• Adrenaline

Question 3

Where are catecholamines produced?

Answer 3

• Produced in chromaffin cells of adrenal medulla of sympathetic nervous system and post-ganglionic fibres of the sympathetic division of ANS

Question 4

What are the functions of adrenergic neurons?

Answer 4

• Synthesis of NA
• Storage of DA and NA in vesicles
• Release of NA
• Metabolism (COMT 20% and MAO 80%)
• Binding to receptors
• Uptake mechanisms (1&2)

Question 5

What are control points in catecholamine action?

Answer 5

1. Biosynthesis
2. Release
3. Uptake (transporters)
4. Receptors
5. Catabolism

Question 6

What is the role of catecholamine reuptake and the three transporters involved?

Answer 6

• Released catecholamines could be taken back into presynaptic terminals
  
  • DAT: dopamine transporter
  • NET: noradrenaline transporter
  • VMAT-2: vesicular membrane transporter

Question 7

Describe the modulation of catecholamine synthesis

Answer 7

1. Neuronal activity increase would enhance the amount of key enzymes at both mRNA and protein levels
2. TH is modulated by end-product inhibition (catecholamine competes with synthesis cofactor)
3. Depolarisation would activate TH activity
4. Activation of TH also involves phosphorylation

Question 8

What is the MOA of tyramine effects?
Where is it found?
MAO inhibitors effects?

Answer 8

• Tyramine can be found in different foods
• When patient is treated with MAO inhibitors, they block the metabolism of NA (increases NA as a result)
• Tyramine is simular in structure to NA - which in addition to MAO blocking metabolism - causes blocking of uptake 1 and blocking the negative feedback of a2 adrenergic receptors